Novel Therapeutics & Delivery Systems

Transcript

• 00:00Cancer therapeutics and delivery systems.
• 00:03My name is Tim Shannon,
• 00:06partner at Canaan Partners venture capital
• 00:09firm that's active in the oncology
• 00:12space in the biotech space in general.
• 00:15And you would like to thank you all
• 00:17for joining us today and what we hope
• 00:20will be a really engaging 90 minutes.
• 00:23I think you know, for those of us who
• 00:25have been involved in in this area,
• 00:28you know there's nothing more exciting
• 00:30than to develop a novel cancer
• 00:32drug and see it benefit patient.
• 00:34It's incredibly rewarding.
• 00:36I think in today's session is some
• 00:40of our speakers present their work.
• 00:43You'll see how impactful Yales Bend
• 00:46in this sphere, and in particular,
• 00:49Yale Cancer Center and really helping
• 00:51to Harold the great progress that
• 00:54we've all seen in Cancer Therapeutics
• 00:57in the last decade.
• 00:59I think Yale on the El Cancer Center
• 01:03recognized that this is really a
• 01:06community effort and requires extensive
• 01:09collaboration networks to make
• 01:11this all work from start to finish.
• 01:14I you know that involves universities,
• 01:17governments,
• 01:17industry as well as investors in all,
• 01:21playing a role in this very
• 01:25important activity.
• 01:27So really,
• 01:27the goal of of today's
• 01:29session is is really twofold.
• 01:31It's for Yale really to continue to
• 01:34broaden that network in that community
• 01:36with whom they engage again to try to.
• 01:39You know,
• 01:40live out their passions of bringing promising
• 01:43and novel therapeutics to patients.
• 01:46But it's also importantly for you
• 01:49in the audience to learn about
• 01:51what Yale has to offer and how you
• 01:53might be able to become part of
• 01:56this community around the El Cancer
• 01:58Center and share that mission and
• 02:01that passion to do great things.
• 02:03So you know some of you may have
• 02:06already been involved in Cancer Center.
• 02:08Some of you this may be your
• 02:10first opportunity,
• 02:11but for both of those groups,
• 02:13we certainly hope it's not the last
• 02:16opportunity in this really catalyzes
• 02:18more engagement with the Cancer Center.
• 02:20Just in terms of some housekeeping issues,
• 02:23you know the audience in
• 02:25general will be muted,
• 02:26so you don't have to worry about the
• 02:29noise you're making in the background,
• 02:31but you know,
• 02:32we really do want this to be interactive,
• 02:35and the chat room will be live
• 02:38and that will be the vehicle
• 02:40with which you know we'd lash,
• 02:42like you to raise questions
• 02:44during the symposium,
• 02:45and particularly for panelists after
• 02:47here with panels, have to say,
• 02:49and your questions can pertain
• 02:51to their comments to there.
• 02:53Your questions can be, you know,
• 02:56really is broad as you like.
• 02:58So again,
• 02:59we would really encourage participation
• 03:02via the chat room that will be open
• 03:05and we will be monitoring this.
• 03:08Finally, this webinar will be recorded.
• 03:10I think I just saw a chat room
• 03:13question come up in that regard so
• 03:15that the webinars being recorded and
• 03:18will be available after the session.
• 03:21So with that introduction,
• 03:23I'd like to welcome our first speaker doctor,
• 03:26Charlie Fuchs.
• 03:27Doctor Fuchs is the Richard
• 03:29and Jonathan Sackler
• 03:31professor of medical Oncology
• 03:33and professor of chronic
• 03:35disease Epidemiology at Yale.
• 03:36He also is the director of the Yale
• 03:40Cancer Center and Physician and
• 03:42Chief of the Smilow Cancer Hospital.
• 03:45Charlie. Thanks very much.
• 03:48Tim, thank you and I want to welcome
• 03:51all of you to our second in this series.
• 03:56Yale engage cancer, which really has
• 03:59been an exciting opportunity for for
• 04:02us to reach out to a broad audience.
• 04:05And I want to just say that you know we're
• 04:08obviously engaged now and a global pandemic,
• 04:10which I think has to some extent been
• 04:12at the forefront of our attention
• 04:15and healthcare and drug development.
• 04:16But, you know, as we get past this and
• 04:19we're all looking forward to that point,
• 04:22we are reminded of the fact.
• 04:24That in the 21st century,
• 04:26cancer is really the great challenge
• 04:29that faces American medicine.
• 04:30It is the focus of so much work
• 04:33clinically in terms of support
• 04:35from government and philanthropy.
• 04:37And really the focus of of investment
• 04:40in drug development.
• 04:41And I think one thing we all share.
• 04:45We are a diverse group on this
• 04:47call from Academia, Pharma,
• 04:49biotech,
• 04:50the investment community where diverse.
• 04:52But I think what we all share
• 04:54in common is a commitment.
• 04:57To innovating in science and taking
• 04:59those discoveries and moving them into
• 05:01meaningful improvements in the treatment,
• 05:04early detection and prevention of cancer.
• 05:06You know, I'm pleased.
• 05:08As the director of the Yale Cancer
• 05:10Center to be at a place with an
• 05:14extraordinary legacy of Cancer Research.
• 05:16Really over the century in cell biology,
• 05:19genetics, chemical biology,
• 05:20pharmacology, immunobiology among others,
• 05:22and in clinical research.
• 05:24And, you know,
• 05:25as the NCI comprehensive Cancer Center
• 05:28for Connecticut in New England that we.
• 05:30We carry that responsibility with great
• 05:33pride beyond the great science we
• 05:35really proud of our clinical programs.
• 05:38In fact,
• 05:38the building I sit in now is
• 05:41the is Smilow Cancer hospital,
• 05:43which is celebrating its 10th
• 05:45anniversary as a center.
• 05:47Now that provides care to 48% of
• 05:50all newly diagnosed cancer patients
• 05:52in the state of Connecticut and
• 05:54patients well beyond that region.
• 05:56And with that has really been
• 05:59the laboratory of moving.
• 06:00Discovery in the laboratory into
• 06:03meaningful clinical treatments for cancer.
• 06:05In fact,
• 06:06one opportunity of great pride.
• 06:08I wanted to share is that this year,
• 06:124 Yale lead clinical trials.
• 06:15Will have led to new approvals in
• 06:18the oncology space with the FDA.
• 06:20So not only we committed to great science,
• 06:24but we're committed to moving
• 06:26that science into the clinic.
• 06:28Ann into ultimate approval.
• 06:29Tim has assembled for today's forum.
• 06:32Just a panel of rock stars
• 06:34who not only do great science,
• 06:36but actually are committed to
• 06:38moving that science into the clinic
• 06:40through their own work and through
• 06:43partnerships by starting companies
• 06:45by working with pharma and biotech.
• 06:47And I think each of their stories are
• 06:50are really going to be interesting for us.
• 06:52I also want to particularly
• 06:54thank Josh Blinker,
• 06:55who's the Chief Executive Officer for
• 06:57locks on Cology for joining our panel,
• 07:00which I think really adds more to
• 07:02the richest of discussion of how you
• 07:04ultimately move drug development from
• 07:06science into ultimate care of patients.
• 07:08You know, one thing we want to do in these
• 07:11forms, and I say this is the second one.
• 07:15The first one was an immuno
• 07:16oncology and very well received.
• 07:18Is in this forum focused on a key
• 07:21aspect of cancer treatment research?
• 07:23Is really that it be conversational
• 07:26we want to. We want interaction
• 07:28not only between our panelists,
• 07:30but with all of you to answer your questions.
• 07:33And more importantly, we want this to
• 07:36be the beginning of a conversation.
• 07:38We hope that this stimulates new partnerships
• 07:41between our colleagues and Yale and you,
• 07:43because ultimately, as Tim indicated,
• 07:45really to make a difference in cancer
• 07:48treatment and Cancer Research.
• 07:49We have to be working together so you know.
• 07:52Please feel free to reach
• 07:54out to me to the panelists.
• 07:56My colleagues both during this
• 07:57meeting and after will remind you
• 07:59of that because we want to work
• 08:01together in this fight against cancer.
• 08:03So Tim,
• 08:04thank you for leading this and I
• 08:06look forward to an exciting forum.
• 08:13Thanks very much Charlie.
• 08:16So the slide you're seeing now
• 08:19reflects the agenda for today,
• 08:22so the way the session will be setup is
• 08:26will have brief 5 minute presentations by
• 08:30the presenters you see listed on the slide,
• 08:34followed by large period of time to
• 08:37enable discussion and question question
• 08:40and answer sessions with panelists.
• 08:43And again, we really encourage
• 08:46your participation here.
• 08:47You know our goal here is really to provide
• 08:51information that you're looking for,
• 08:53so your questions are really what
• 08:55we need to help deliver that to
• 08:58you in their presentations.
• 08:59Each of the speakers will
• 09:01talk a little bit about,
• 09:03you know what their course
• 09:05scientific expertise is an in,
• 09:07particularly what?
• 09:08What sort of questions they are trying
• 09:11to answer with the goal again of
• 09:13ultimate impacting cancer care in their
• 09:16presentations and in part of the comments.
• 09:18Again, they also talk about.
• 09:20Some of the ways they have collaborated,
• 09:23you know,
• 09:24to to accomplish what they've
• 09:26accomplished thus far,
• 09:27but also set up the stage for
• 09:29additional ideas about collaboration
• 09:31with the broader community.
• 09:33So the chat room will be open throughout.
• 09:36Please again,
• 09:36feel free to put your questions into
• 09:39the chat room and will be monitoring
• 09:42those and bring those forward.
• 09:44And again all speakers will start
• 09:46with about a 5 minute presentation
• 09:48before we move into discussion.
• 09:50And the question and answer session.
• 09:54So with that,
• 09:55I'd like to welcome our first presenter,
• 09:58Ranji Vendra. Angie.
• 10:01Great,
• 10:02thanks
• 10:02so much for having me today and
• 10:04thanks everyone for joining and I'm
• 10:06a professor of therapeutic radiology,
• 10:08the Yale School of Medicine and also Co.
• 10:10Director of Yale's Brain Tumor
• 10:12Center will go on to the next slide.
• 10:15So one thing I'd like to start with
• 10:18this Doctor, Fuchs mentioned is is.
• 10:20We have quite a presence
• 10:21along the translation.
• 10:22ULL research spectrum at yeah,
• 10:24and it's I've been here both as a medical
• 10:27student and is a 9th year into faculty
• 10:29and it's just a wonderful place to be.
• 10:31On one end we have disruptive cutting
• 10:34edge science and just just a few examples
• 10:36that you won't hear about today,
• 10:38but I wanted to highlight
• 10:39Jason Crawford and Seth Herzon.
• 10:41Finding gut bacteria that produce entirely
• 10:43new DNA damaging agents in the middle there.
• 10:45Mark Saltzman, Dawn Engelmann.
• 10:47Peter Glaser with nanoparticles
• 10:48and tumor targeting peptides.
• 10:49At the bottom there we have
• 10:52from Aaron Rings lab,
• 10:53an entirely new secrete immune checkpoint.
• 10:56But on the other side of the spectrum we
• 10:58also have we're known for pivotal studies
• 11:01and excellence in clinical research.
• 11:03Here is the study.
• 11:04Two studies showing Biden Patrylak
• 11:06and Roy herbs,
• 11:07and also work from Pat Larusso,
• 11:09really defining high level clinical
• 11:11trial designs.
• 11:12And behind and in parallel to all that,
• 11:14we have a very vibrant and active
• 11:16biotech and form a community.
• 11:17And it's really driven by the heart of it,
• 11:20of at the at the Yale Office of
• 11:22Collaborative Research and certainly
• 11:24can check out their website and you
• 11:26can see there just some logos of the
• 11:28companies that have been recently
• 11:29started and notable that some of
• 11:31these companies are associated
• 11:33with the papers that I just showed
• 11:34you earlier and will be talking
• 11:36about some of this work throughout
• 11:38the sessions today and then we'll
• 11:40move on to the next slide.
• 11:43So just a little bit of background about me,
• 11:46so I sort of also live in multiple nodes
• 11:48of that research translational spectrum.
• 11:50I'm P of an NIH funded DNA repair lab,
• 11:52and our lab is mainly focused on oncology,
• 11:55synthetic lethal drug screening with
• 11:56a focus on DNA repair metabolism,
• 11:58and we've been fortunate to publish a
• 12:00number of high impact stories recently.
• 12:02In some of those journals shown there.
• 12:04I'm also a radiation oncologist and is
• 12:06a Co director of the Brain Tumor Center.
• 12:08I'm involved in a lot of glioma
• 12:10clinical trials.
• 12:11These are some of the cooperative
• 12:13groups that we work with.
• 12:14Here at Yale and then sort of on
• 12:16the evenings and weekends and very
• 12:18much involved in the biotech world
• 12:20and an active biotech entrepreneur.
• 12:21Most notably some accompany you may be
• 12:23aware of a Cybex therapeutics which
• 12:25will be in the clinic early next year,
• 12:27will go to the next slide.
• 12:31So just wanted to give you really just
• 12:34two case studies of some of the work
• 12:36that we are doing and how we've been able
• 12:39to translate that from the bench into
• 12:41the bedside and really into biotech.
• 12:43This is a story that we recently
• 12:45published in Science Translational
• 12:46Medicine and then more recently in
• 12:48nature and Nature Genetics where we
• 12:50found that alqama tablets like ID H1
• 12:52mutations that induce two HG unexpectedly,
• 12:54causing our defector Bracken.
• 12:55This defect that causes PARP
• 12:56inhibitor sensitivity, and we made
• 12:58that discovery just a few years ago,
• 13:00and it's really collaborative effort.
• 13:02Across multiple labs here at Yale,
• 13:03including Peter Glaser,
• 13:04Moroccan Alan Stuffing Helene.
• 13:05But we've been fortunate to be able to
• 13:08rapidly translate that into the clinic,
• 13:09and these are some of the trials
• 13:11that are shown here.
• 13:13But most importantly,
• 13:13in the bottom right,
• 13:15those are the clinical trials
• 13:16that yell that really made these
• 13:18these clinical protocols possible,
• 13:19and we're now taking specimens from
• 13:21these trials and bringing them back
• 13:23into the lab to try to understand who
• 13:25responds and who doesn't and what's
• 13:26the molecular basis for that response.
• 13:29Patterns on the next slide.
• 13:32And just a second more recent
• 13:33story that we published in Nature,
• 13:35Communications on the metabolic front,
• 13:37we found that a phosphatase which is
• 13:39up regulated or mutated in a number
• 13:41of cancers, including brain tumors,
• 13:43actually has an epigenetic
• 13:44silencing function that had not
• 13:46been described previously.
• 13:47And this leads to silencing of Aki
• 13:49nad metabolism gene called NAPER,
• 13:51which essentially inactivates the press
• 13:52handlers salvage pathway shown there
• 13:54and leads to exquisite sensitivity to
• 13:56class of drugs called nampt inhibitors.
• 13:57Now these drugs have actually been
• 13:59tested extensively in clinical trials,
• 14:01and many of them.
• 14:02Have been shelved or stymied
• 14:03because of lack of good biomarkers,
• 14:05and we actually believe we have
• 14:07those biomarkers now and again.
• 14:08Leveraging the yellow CR in the Blatnik Fund,
• 14:10which we can get to later
• 14:12in Connecticut innovations.
• 14:12A local state backed VC and the pitch
• 14:15program developed by Craig Cruz,
• 14:16we've been able to start a company,
• 14:18developed a new class of nampt
• 14:19inhibitors and we hope to bring
• 14:21those in the clinical trials soon.
• 14:22So with that,
• 14:23that's just the flavor of what we
• 14:25do and really looking forward to
• 14:27the discussion today and thank you.
• 14:37Thanks, Ron G much appreciated.
• 14:41Will save again. Collect questions
• 14:43throughout the presentation.
• 14:44So now we'd like to move on to
• 14:47the presentation of CD10 CD.
• 15:21Can you please turn on
• 15:22your video if you're able.
• 15:47Siri, can you unmute and open your video?
• 15:54Tim, maybe we could advance
• 15:55to Craig slides and give City
• 15:57a chance and we can come back a city in a
• 16:00moment. Sounds like a good idea.
• 16:02So again, we'll come back to see Chan,
• 16:05but let's move on to Craig Cruise while
• 16:09we try to workout CDs kinks. Great
• 16:13by the way I go. Thanks Tim.
• 16:17So I am the John C Malone professor
• 16:20of Emccd and joint appointment
• 16:22in pharmacology as well as in
• 16:25chemistry and I'll be talking a
• 16:27bit about my role in running the
• 16:30Yale Center for Electro Discovery,
• 16:32which is the small molecule an RNA eye
• 16:36screening center that is here at yeah.
• 16:39Excite please.
• 16:41So I've been here for 25 years working at
• 16:44the interface of chemistry and biology.
• 16:47When I started here,
• 16:48it was primarily focused on motive,
• 16:51action studies of natural products,
• 16:53and this is 1 molecule that
• 16:55came from those efforts.
• 16:57It is a derivative of a microbial Organism,
• 17:00derived Organism, excuse me,
• 17:02compound that is a antitumor
• 17:04compound that is a producer,
• 17:06monitor and so my lab identify the
• 17:08mode of action of this molecule,
• 17:11did some additional chemistry.
• 17:13I found it my first company.
• 17:15Pretty Alex 17 years ago that turned this.
• 17:21Yale finding into a drug candidate and
• 17:25this was approved for relapsed refractory
• 17:28multiple myeloma in 20 twenty 2012.
• 17:31Pretty,
• 17:31Alex was purchased by Onyx and
• 17:34ultimately by Amgen and Kyprolis
• 17:36now does over a billion dollars in
• 17:38sales for again refract refractory
• 17:41relapsed multiple myeloma,
• 17:42but since then next slide I've been
• 17:45working on the flip side of that.
• 17:48Not blocking degradation but
• 17:50actually inducing degradation,
• 17:51and so my last played a key role in
• 17:54developing this new field of targeted
• 17:57protein degradation where we can
• 17:59through induced proximity drag proteins.
• 18:02To the quality control machinery of the cell,
• 18:05inducing its degradation.
• 18:06And I've been working on it for 20 years now,
• 18:11but a key part of this transition
• 18:14in terms of translational impact
• 18:16was the founding of our Venice
• 18:19here in New Haven in 2013.
• 18:22This is from their IPO in 2018.
• 18:25They now have two clinical
• 18:27candidates in trials,
• 18:28one for breast and went for prostate,
• 18:31and Moreover,
• 18:32at least for their leading one,
• 18:35the prostate enable been able to
• 18:37demonstrate that this technology.
• 18:39Works in humans with respect to
• 18:42actually targeting and decreasing
• 18:43surrogate markers for prostate,
• 18:45and so those quite quite exciting.
• 18:49And I continue to play a role
• 18:51in advising our business,
• 18:53but I wanted to spend just a little
• 18:55bit of time talking about another
• 18:58hat that I wear on the next slide.
• 19:01And that is the Yale Center
• 19:03for Molecular Discovery,
• 19:04founded in 17 years ago.
• 19:06And this is the really the nexos
• 19:09of translational research at
• 19:10Yale with respect to developing
• 19:12assays screening compounds,
• 19:13you can go on to the next slide.
• 19:17And so we have the resources where
• 19:19we have small molecule compounds.
• 19:21We have RNA Sir and a collection,
• 19:24so you can go back to sleep.
• 19:28Now forward and so we have a
• 19:32team of professionals that are
• 19:34helping the Yale researchers to
• 19:37translate their academic findings
• 19:39into assay and thin screening.
• 19:42Small molecules.
• 19:43As I using robotics and then
• 19:46helping to interpret those assays
• 19:49and those results with the whole
• 19:53point of coming up with impact.
• 19:56And that is defined by
• 19:59papers as defined by grants.
• 20:01But it's also defined by starting companies,
• 20:04so where we stand now is that
• 20:06we have the infrastructure.
• 20:08We have the network, we have the resources,
• 20:11but we want to reach out to establish
• 20:14more industrial partners to help guide us.
• 20:17Help prioritize, help help direct where
• 20:19we should be focusing our efforts.
• 20:21You know what are the unmet
• 20:23needs an industry?
• 20:25What are the new indications
• 20:26that we're not aware of,
• 20:28and so we're really like to
• 20:31serve as a bridge?
• 20:32If you will, between?
• 20:34The diverse collection of cancer
• 20:36researchers at Yale and the greater World.
• 20:39And so.
• 20:40With that,
• 20:41I'll stop and turn it back to Tim.
• 20:50Thanks Greg.
• 20:51So I think we have City chance.
• 20:55Logistics worked out.
• 20:56An will go back to City
• 20:59Chance Presentation, City.
• 21:01Can everyone hear me?
• 21:06Good OK thanks. Next slide.
• 21:12So are my laps focus by Mary.
• 21:17Is cancer email therapy and we are trying
• 21:20to use multiple approach to improve
• 21:23cancer immunotherapy which is currently.
• 21:26A transformative therapeutic modality,
• 21:28but still made a having major setbacks by
• 21:33more than 70% of patients not responding.
• 21:36So the first program for us is to
• 21:40discover novel immune checkpoints
• 21:43or T cell regulators that are.
• 21:46Are important for the team might be
• 21:49environment and in order to overcome
• 21:52the current therapy resistance.
• 21:54An once those new molecules will
• 21:56discover we will be able to identify
• 22:00the therapeutic strategy for them and
• 22:03then the second program to engineer
• 22:06immune cells themselves like car T
• 22:09cells and develop therapeutic strategy
• 22:12to infuse those cells back to patients
• 22:15and as a cell therapy modality.
• 22:18In the final one would be program
• 22:21based on cell and gene therapy,
• 22:23and in this case we call it Meiji,
• 22:26which I'll elaborate later on next slide.
• 22:31So Major is a new class of
• 22:35cancer immunotherapy.
• 22:36We believe even though he said early stage,
• 22:40it is coin as Multiplex
• 22:42activation of endogenous genes,
• 22:45as immunotherapy may I maging so we
• 22:48think this is a new strategy as compared
• 22:52to order over the existing ones,
• 22:55because cancer cells.
• 22:57They have a lot of signals that
• 23:00are considered non self meaning.
• 23:03Mutations that distinguish them
• 23:05from the normal cells.
• 23:06But in order to find and kill
• 23:09the cancer cells,
• 23:10we better off amplify such signals in
• 23:13one of the most efficient way we did.
• 23:16Figure out is by crisper activation,
• 23:18just crank up all the non self signal
• 23:21so the immune system can see the
• 23:24cancer cells clearly and then come
• 23:26to destroy the cancer cells and
• 23:28take off the new cycle next slide.
• 23:32And then we have done a few proof
• 23:35of principle experiments and so
• 23:36that these works quite well in the
• 23:39preclinical models across multiple
• 23:41cancer types, including a pressman,
• 23:43normal pancreatic cancer types.
• 23:45And.
• 23:46We hope to continue to translate
• 23:49these knew fair treatment modalities
• 23:51and use them either alone or in
• 23:55combination with what already available.
• 23:59Thanks.
• 24:05I guess that he. Next,
• 24:07we'll go to Offei Rogers and
• 24:10listen to the presentation
• 24:13of her work, right?
• 24:17Thank you Tim. So I am an
• 24:19associate professor in the
• 24:20Department of Therapeutic Radiology and
• 24:22my lab focuses on understanding DNA
• 24:25damage response and so I like to tell
• 24:27you a little bit about how we've been
• 24:29using that interest to develop a novel.
• 24:34Next slide, please.
• 24:38So Uncle Gene Amplification is
• 24:40considered to play major roles not
• 24:43only in the formation of cancers.
• 24:45By amplifying genes that
• 24:46provide glued advantages,
• 24:47such as increased cell proliferation,
• 24:49angiogenesis, and decreased apoptosis,
• 24:51but also in later progression to states
• 24:54of that accesses by amplifying genes
• 24:56that facilitate migration and invasion.
• 24:58So it's not a surprise that gene
• 25:01amplification has become an
• 25:02important therapeutic target in the
• 25:04development of precision medicine,
• 25:06and so the current drug
• 25:08development strategy has been to.
• 25:10Target the overexpress protein products
• 25:12that are produced due to gene amplification,
• 25:15which has resulted in major drug
• 25:18breakthroughs such as Herceptin and
• 25:20other tyrosine kinase inhibitors,
• 25:21and so our lab as I said to you before,
• 25:25is really interested in understanding
• 25:27DNA damage response,
• 25:29and we have taken an approach to
• 25:31manipulate the DNA damage response
• 25:34network in order to find a novel way to
• 25:37treat these types of cancers so the cell.
• 25:40Has already in place DNA damage response.
• 25:45Mechanisms in order to conserve genomic
• 25:48integrity and our goal is to hope to
• 25:52manipulate this network by forcing
• 25:54cancer cells to go towards pathway
• 25:56on the pathway on the right following
• 25:59excessive DNA damage to activate a
• 26:02pop ptosis as opposed to normal cells
• 26:05which can choose to repair DNA damage.
• 26:08And so by hijacking the cell zone machinery,
• 26:11our goal is to reduce the normal
• 26:14tissue toxicity that might be
• 26:16experienced by these kind of drugs
• 26:18and prevent off target effects.
• 26:20So next slide please.
• 26:24So our.
• 26:25Focus has been to directly convert
• 26:28the amplified DNA into DNA damage
• 26:30and so by doing so we have designed
• 26:34oligonucleotides that can bind to
• 26:37specific sequences within the amplified gene,
• 26:41which is then forms a triplex structure
• 26:44that is recognized by the cell's
• 26:47DNA damage and through replication
• 26:49stress leads to excessive DNA damage,
• 26:52specifically,
• 26:53at the amplified regions this
• 26:55excessive DNA damage.
• 26:56Then can activate a DNA damage
• 26:59response as a result of all this
• 27:02damage leading to the activation
• 27:04of a P53 independent pathway,
• 27:07and so we believe that this drug
• 27:09design platform can actually have
• 27:12far reaching approaches due to the
• 27:14fact that there are over 500,000
• 27:17unique triplex targeted sequences
• 27:19throughout the human genome,
• 27:21and in fact there are more than
• 27:24460 amplified genes are cross
• 27:2614 different cancer subtypes.
• 27:28So we believe that we can specifically
• 27:31use this drug design platform to target
• 27:34many different types of cancers that
• 27:37are characterized by gene amplification.
• 27:40And thank you.
• 27:47Thanks very, very interesting.
• 27:49So now we move on to the final
• 27:53speaker who's joined our panel
• 27:55today and that's Josh Blinker.
• 27:58Josh comes from outside of Yale,
• 28:01but he certainly is part of the community
• 28:05living in Connecticut Ann and starting
• 28:08his last company here in Connecticut.
• 28:11So we're thrilled to have him here.
• 28:14Josh can really speak to today's
• 28:17topic from a number of angles.
• 28:20You know, given his background,
• 28:23so he's a trained medical oncologist.
• 28:26He's worked at the FDA.
• 28:28He's worked in venture capital and
• 28:31then most recently he's started his
• 28:34own incredibly highly successful
• 28:36company locks in one Cology,
• 28:38which recently was acquired by Lily.
• 28:41So now he sits inside Eli Lilly
• 28:44and is really one of the senior
• 28:48managers there in charge of.
• 28:50Well, is strategy and oncology,
• 28:53so again,
• 28:54we're really pleased to have Josh
• 28:57here today and he'll just offer
• 29:00some comments on what he sees is the
• 29:04challenges and opportunities and
• 29:07developing novel cancer Therapeutics
• 29:10an in regard to collaborations
• 29:12of companies and academia,
• 29:15Josh?
• 29:16Thanks
• 29:17Tim for the con introduction
• 29:19and having me here I.
• 29:21Prepared, prepared like two sets of remarks.
• 29:25And I think one of them may be
• 29:27appropriate for this session.
• 29:29I might save the other,
• 29:30but I'll try to get them to quickly Tim.
• 29:33And if you want me to elaborate on anything,
• 29:36please interrupt me or come back at the end.
• 29:39But one set of remarks I thought
• 29:42might be interesting and relevant to
• 29:44the attendees is the topic of what
• 29:46are the types of relationships and
• 29:48academic lab can have with industry?
• 29:50And what are the sort of risk rewards
• 29:52and implications of those relationships?
• 29:54And I really.
• 29:55Break them into sort of 3 three buckets with
• 29:58sort of increasing levels of intensity.
• 30:01I think at the in the sort of
• 30:04lightest intensity relationship,
• 30:05said is,
• 30:06I'll call it the advisor expert model,
• 30:09where the goal of the relationship with
• 30:12industry is really to raise awareness
• 30:14or detract resources in a global sense
• 30:17to a problem set that you or your lab
• 30:20thinks is important to human disease.
• 30:22And you can have this influenced by say.
• 30:26Riding free,
• 30:26free advice even or providing paid
• 30:29expert advice as a retained consultant.
• 30:32Or maybe being a scientific advisory
• 30:35member to accompany or small company or
• 30:38large company or guest lecturer in a
• 30:41large pharma setting is another example
• 30:44and the output that you're expected
• 30:47to supply whether there is sort of.
• 30:50Compensation return or not
• 30:51is basically your ideas.
• 30:53Alot of your remarks are going to likely
• 30:55refer to public domain information,
• 30:58but it's really your expertise and
• 31:00again the goal from both sides is just
• 31:03to bring awareness and education to
• 31:05perhaps a biology set of questions
• 31:08that needs your particular input,
• 31:10so that's that's level one that's light.
• 31:12That's no strings.
• 31:14That's kind of easy to come and go with,
• 31:17and I suspect many of you have
• 31:20already engaged.
• 31:20In that type of relationship.
• 31:23One level up from that.
• 31:25Is probably the media's,
• 31:27then I'll just call it for lack
• 31:30of a better sort of bucket term,
• 31:32let's call it some kind of sponsored
• 31:35research agreement that covers
• 31:37you and your lab or your group.
• 31:39And in probably involves your,
• 31:42you know your University signing
• 31:43off and in this type of agreement,
• 31:46the expectation is that your lab
• 31:48or know how is providing some kind
• 31:51of assay expertise where there's
• 31:53a data readout expectation that.
• 31:56That is awesome.
• 31:57What's proprietary you know between
• 31:58you and the industrial partner.
• 32:00And I've seen this transpire in both.
• 32:03What I'll call an external model and
• 32:05an internal model, the external model.
• 32:07There's a,
• 32:08there's a transference of the
• 32:10assay to the partner, they run,
• 32:12the assay,
• 32:12they perhaps share the results back with you,
• 32:15but your academic lab mission is not
• 32:18asked to be amended to supply the data.
• 32:21Ultimately it sits on the part of
• 32:23the industrial sponsor to do that,
• 32:25but you've enabled the tech transfer
• 32:27of that assay.
• 32:28And then on the internal relationship your.
• 32:33You're really the one running the assay,
• 32:35and therefore you're kind of on the
• 32:37hook for deliverables and you have
• 32:39to balance the academic mission
• 32:41with the Industrial Partnership and
• 32:43how to staff that and resource it.
• 32:45But either way that the goal
• 32:48here is to create data,
• 32:50not just your ideas and those data.
• 32:53Again, our internal or externally generated,
• 32:55and then the third level is probably the most
• 32:59intense that's co-founder or cofounder role,
• 33:02where it might subsume
• 33:03the other two categories.
• 33:05There might be a sponsored
• 33:07research component.
• 33:08There might be an advice component,
• 33:11but really,
• 33:11you're really putting your kind of currency,
• 33:14your personal currency,
• 33:16behind a set of ideas.
• 33:18And there's some expectation
• 33:21that that commitment.
• 33:23With all its conflicts and my next
• 33:26set of remarks tries to handle
• 33:29some of those conflict issues.
• 33:31But really,
• 33:32the behavior involves you know your
• 33:34personal sort of stake in this thing,
• 33:37and you might be involved in
• 33:40mediating conversations with check,
• 33:41transfer or investors or
• 33:43entrepreneurs as they come around.
• 33:45That idea or pharma executives.
• 33:47If it's a big pharma
• 33:49relationship or subsidiary,
• 33:50so I think that's the
• 33:53most intense and I think.
• 33:55It it has its own tradeoffs,
• 33:57but but with that I'll pause
• 33:59and see if Tim you'd like
• 34:01me to stop or elaborate.
• 34:05Josh, I think you're gonna run.
• 34:07Why don't you spend another minute
• 34:09or two elaborating and then will
• 34:11then next look for some panel
• 34:13reaction to your comments so can
• 34:15tune on a little bit more. Alright.
• 34:19It might be too much to handle
• 34:22the complexities of you know.
• 34:25I'd like to have sort of a dedicated
• 34:28sensor set of remarks about the
• 34:32frictions that I see as academics.
• 34:35Uh. Is academics?
• 34:37Really set up one of these three
• 34:41relationships and how do they?
• 34:45I'm just being distracted by some
• 34:48inappropriate comments on my.
• 34:50Screen, maybe I'll ask the
• 34:52moderator to look into that.
• 34:54My apologies were taking
• 34:55care of that now, OK.
• 34:59You know, I think I think it
• 35:01all of these relationships sets
• 35:02involve some soul searching,
• 35:05which I think happens at 2 levels.
• 35:07That happens at the personal level.
• 35:09Like what am I comfortable with?
• 35:12How do I want to use my time?
• 35:15How do I feel comfortable,
• 35:17uncomfortable with the idea of industry
• 35:19being part of my academic mission?
• 35:21And then I think there's also
• 35:23a time management, you know,
• 35:25sort of implication to some of this.
• 35:28How do how do I want to? Spend my time.
• 35:32Do I like the idea of being around a company?
• 35:35Do I like the idea of being in the
• 35:38halls of a large pharma periodically?
• 35:40So you know, I think.
• 35:44I think it all looks like roses.
• 35:46I think.
• 35:47I think the the worst assumption set
• 35:49to go in with is like OH industry
• 35:52is this sort of undisciplined,
• 35:54unlimited source of capital
• 35:56that's just going to augment
• 35:58the academic mission of my lab.
• 36:00I think that's the most simplistic
• 36:02and quite honestly unhelpful
• 36:03for both parties mentality,
• 36:05and it's a very common mentality.
• 36:07I encounter an I don't, I don't.
• 36:10I think it's sort of a dishonest partnership.
• 36:13If that's the thesis,
• 36:14because it misunderstands.
• 36:15What I think the true value of the
• 36:18partnership was intended to be,
• 36:19and so happy to unpack that a little more.
• 36:22But I want to say it out loud,
• 36:25because if one listening to
• 36:26this had that expectation,
• 36:28I think it's really worth another
• 36:30set of discussions that maybe
• 36:31the panel wants to unpack.
• 36:40Great thanks Josh. So that's yeah.
• 36:44A great entry into our panel discussion
• 36:47so we could just ask all the panelists,
• 36:51open up their mikes and turn on
• 36:55their videos and. Will move into.
• 36:59The discussion session. Of the meeting.
• 37:03So again reminder to the audience it.
• 37:07Please bring forward any questions
• 37:09you want into the chat room.
• 37:12Again, we'd very much like to hear those,
• 37:16so let me maybe just start out by
• 37:20asking the panelists just to react
• 37:23a little bit to Josh's comments.
• 37:27And in terms of your experiences in terms
• 37:31of interactions with investors about tech.
• 37:34For Pharma and maybe comment a little
• 37:36bit on how you thought about that.
• 37:39As you've sort of entered into those
• 37:42relationships and how you've managed some
• 37:44of those issues and some of those tensions.
• 37:51I I, I think that
• 37:53Josh should bring up a good point
• 37:56in terms of just expectations on the
• 37:59faculty's part in terms of what they
• 38:02hope to get out of these relationships.
• 38:05I like to think that that isn't that
• 38:08big of a problem with these days.
• 38:11It has been a problem in the past,
• 38:14but OCR and the entrepreneurial
• 38:17ecosystem at Yale does a really good job.
• 38:20I feel in terms of educating faculty.
• 38:23And helping them set expectations,
• 38:25figure out what's possible and
• 38:27so at least compared to when I
• 38:30started again 25 years ago,
• 38:32I find that the younger faculty that
• 38:35are now thinking about these types of
• 38:38partnerships are much more sophisticated
• 38:40in terms of what they need to prove with
• 38:44respect to what they bring to the table,
• 38:47so I'm sure that there will
• 38:49always be exceptions,
• 38:51but I've been impressed.
• 38:54Thanks Greg. And Elsa Ranjit,
• 38:57any comments in a youth? Sort of.
• 38:59Been involved in some of these
• 39:01situations, so yeah, it's
• 39:03a really great great question and I've
• 39:05been involved in a lot of different levels,
• 39:08including the companies that I've
• 39:10started and also companies have
• 39:12reached out to me and there really
• 39:13is a sweet spot I found. I'm I've.
• 39:16I've found that some smaller companies
• 39:17in larger companies really understand,
• 39:19as does the academic side.
• 39:21You know, the balance in the symbiosis
• 39:23of what each party can offer an
• 39:26you know if you can get it right,
• 39:28you can, really, you know.
• 39:30The academic and offer expertise or
• 39:32think about things the way the farmer,
• 39:34farmer, biotech side wouldn't
• 39:35necessarily an really vice versa.
• 39:37So I think it's there's an art to it,
• 39:40and I think it's actually quite
• 39:42important to recognize really.
• 39:43A lot of comments that Josh said so.
• 39:48But my Sanji, who said that anyone
• 39:50else with any comments or thoughts?
• 39:53I mean, I think it's important
• 39:55guidance and really these interactions,
• 39:58like all interactions,
• 40:00require trust and familiarity and and
• 40:03really are based on relationships.
• 40:05That was a part of the
• 40:08purpose of meetings like this.
• 40:10Again, is to build those relationships
• 40:13again to sort of navigate those.
• 40:16Those inherently or potentially
• 40:19tricky issues between an academic
• 40:21scientist and an investor or.
• 40:23Industry. Um? Let me say so.
• 40:27We have some questions coming in,
• 40:29so let's move to some
• 40:31questions from the audience.
• 40:32The first one I'll just read out.
• 40:36As an investor,
• 40:38I'm intrigued by the YMCD.
• 40:40Is this facility and the professionals
• 40:44working there accessible to people
• 40:47start up companies outside of Yale?
• 40:50Yeah,
• 40:51no I can. So the answer is yes,
• 40:55we have mechanisms in place that allow
• 41:00the screening technology, robotics,
• 41:02the compounds they actually development.
• 41:05At at at prices that are of course
• 41:08consistent with hail policy.
• 41:10But yes, it is possible.
• 41:12In fact, several startups Yale based
• 41:15startups use this as a way to augment in
• 41:18a virtual way some of their challenges
• 41:21of just getting off the ground.
• 41:23And so it really I think, is nice bridge
• 41:27again to translational work from you.
• 41:32Thanks Greg. Another question, can
• 41:35I interrupt one second I I want to
• 41:37apologize to the panel and the audience.
• 41:39There was obviously some individuals
• 41:41who are disruptive and posting
• 41:42it totally inappropriate things,
• 41:43and I know the Kathy Lynch and
• 41:45her team are working to remove it,
• 41:47so I just want to apologize for what is
• 41:50a great forum and I'm sorry to interrupt,
• 41:52but I just wanted to explain that.
• 41:56Appreciated Charlie and and
• 41:58we will carry on for sure.
• 42:01Make sure we pick up the the
• 42:03appropriate questions from the chat
• 42:05room so one of these phase was for
• 42:08you and I don't know if you saw it,
• 42:11but I think again,
• 42:12people find you know the basis of your
• 42:14approach and the potential scale of
• 42:17your approach to be really interesting.
• 42:19So the question really was framed around,
• 42:21you know, potential downsides of
• 42:23this in regard to toxicities and how
• 42:26that might be able to be managed,
• 42:28but maybe could you just how you think
• 42:31about that in terms of measuring
• 42:33the toxicities and also maybe.
• 42:35On delivery,
• 42:35so how would you think about delivering
• 42:38these therapeutics to target tissues?
• 42:41Yes,
• 42:41I think the beauty of our approach is
• 42:43the limitation of having toxicities.
• 42:45So you might imagine if we decide on
• 42:48oligonucleotide to bind to a specific
• 42:50sequence within a gene that in a normal
• 42:53cell you would only have one or two copies,
• 42:56and I'll use her too. As an example,
• 42:58a normal cell you would only have one
• 43:01or two copies of the her two gene,
• 43:04meaning there would be only two binding
• 43:06events within that normal cell at the most,
• 43:09and that this kind of DNA.
• 43:11Damage would be effectively repaired
• 43:13by DNA damage response pathways that
• 43:16we know can recognize and repair
• 43:18this type of DNA damage.
• 43:19Conversely,
• 43:20in a cell that has gene amplification,
• 43:23there would be multiple binding events.
• 43:25The induction of excessive DNA damage that
• 43:28would then overwhelmed the repair capacity,
• 43:30and so the cell will then choose as an
• 43:34alternative to activate a pop ptosis.
• 43:36So I think that that is the beauty
• 43:39of our approach because.
• 43:41It takes advantage of the cells
• 43:43genomic integrity and those pathways
• 43:45that put in place to maintain that
• 43:48so normal cells can repair.
• 43:49They will survive and they will be fine,
• 43:52while the amplified cancer genes
• 43:54would have excessive DNA damage
• 43:56and they would should choose to
• 43:58activate their own cell death.
• 44:00In regards with regards to delivery,
• 44:03we have been working with Doctor
• 44:06Mark Salzman an have been able to
• 44:09use nanoparticles to affectively
• 44:11deliver these oligonucleotides
• 44:13to specifically to tumors,
• 44:15and we've been very successful with this.
• 44:19Using the nanoparticles,
• 44:20we have very good uptake of
• 44:23our oligonucleotides to tumors.
• 44:27Alright, thanks very much,
• 44:29I appreciate that. Yeah,
• 44:31next question comes from the inside.
• 44:33Think is is again a bit of a follow up on.
• 44:38You know, the potential
• 44:40academia industry tensions.
• 44:41So you know, maybe the question we go
• 44:44to out to each of the academic pies.
• 44:47How do you manage? You know,
• 44:50sort of euryale responsibilities of
• 44:52training and developing students.
• 44:53PHD's post docs, you know with issues
• 44:56that pertain to your corporate relationships.
• 44:58Maybe talk a little bit about how
• 45:01you all just manage those issues
• 45:03within your lab in terms of who
• 45:06you know isn't my pretentious
• 45:08sort of who's involved in purely
• 45:10or academic work versus who might
• 45:12be involved in an industry work.
• 45:15So let me just open that up for anyone.
• 45:21Great, I'll jump in first. You
• 45:23know, actually 1 one thing that I've
• 45:25learned in the recent years is that you
• 45:28know a lot of trainees have different
• 45:30aspirations in different interests,
• 45:32and you know it's not.
• 45:34You know you'll have graduate
• 45:36students and postdocs,
• 45:37especially in these times that aren't.
• 45:39You know, may have an academic focus
• 45:42for their career, may have pharma,
• 45:44biotech, startup consulting,
• 45:45venture capital and actually now often will.
• 45:48When I have career development discussions,
• 45:50I actually first ask my trainees.
• 45:52Where do you want to be?
• 45:54And you know there's no no judgment
• 45:56about where you know every part of this
• 45:58life science development process is
• 46:00very important and it will help me know
• 46:02what you want to do in your career,
• 46:04because that actually also helps me.
• 46:06How much to involve some of
• 46:08our trainees when appropriate?
• 46:09Obviously, in some of some of
• 46:10the work that we do outside of,
• 46:12you know outside of Yale,
• 46:14I think that that you know I'll
• 46:16leave it at that as a first comma,
• 46:18but let some other
• 46:19folks comment as well.
• 46:22Anyone else wanna add?
• 46:29I can simply say that way I enter
• 46:32these collaborations partnerships.
• 46:34I always make it clear.
• 46:36And of course, Yale requires that work
• 46:39that's done in my lab has to be published.
• 46:43A bowl with. Of course.
• 46:45The write write reviews and checks and
• 46:48balances, but it has to be in theory,
• 46:52publishable. But to Rungis point,
• 46:54you know, I find that there's
• 46:57a wide spectrum of people.
• 46:59Wanting to sample industry and in
• 47:02fact I think that's a big knock
• 47:05against academia right now is that
• 47:07we are don't do enough to offer
• 47:10them real world opportunities,
• 47:12so I find that these relationships that
• 47:14I have with the private sector actually
• 47:17help my lab in terms of recruiting people,
• 47:21people that want to learn how industry
• 47:24works and specifically you know
• 47:27what type of skill sets they need
• 47:29to or can pick up while in my lab.
• 47:32And so I find that it is a really
• 47:35nice balance,
• 47:36but I haven't had a problem in
• 47:39terms of students.
• 47:40And maybe it's because there's
• 47:41a selection there.
• 47:42They come to my lab wanting
• 47:44specifically to gain that skill set.
• 47:48Yeah, great anyway I'll just add.
• 47:52You know local here in involved a bit
• 47:54to speak to that hunger and interest.
• 47:56You know we had came in with both
• 47:58Yale and UConn have started at.
• 48:00Yeah, what's called the Yale
• 48:02Canaan Fellowship program.
• 48:03Which really you know is open to
• 48:06MD or PhD students who are really
• 48:09interested in in the more corporate
• 48:12side of this bit and startup
• 48:14biotechs or on the investment side.
• 48:17And again the interest in that
• 48:19program is exquisite and that
• 48:22the talent is frankly outrageous.
• 48:24So again, I think there are certainly
• 48:28are large segments of the new
• 48:31world of Chinese who overly Archana
• 48:33learn this other side of the.
• 48:36Up the universe early on in their careers,
• 48:38and I think it's great because I
• 48:40think the less this is sort of a 2
• 48:43sided game and the more it's just
• 48:44the continuum and I think that
• 48:46much more productive it will be in
• 48:48frankly needs to be a continuum.
• 48:50Obviously with appropriate
• 48:51precautions to protect.
• 48:52You know academic integrity,
• 48:54but you know,
• 48:55I think the world would
• 48:56be a far better place.
• 48:58You know more seamless.
• 48:59We can sort of make make this for people.
• 49:03Throwback to you,
• 49:04I mean you
• 49:06can you as
• 49:07I've mentioned,
• 49:08have you know real wide aperture and?
• 49:11In terms of what you know what you've gone,
• 49:15you know your work experiences and
• 49:17your success is I'm just curious
• 49:19now as you sit inside,
• 49:21you know one of the largest
• 49:23pharma companies and you really
• 49:25have oversight in terms of.
• 49:27In a lot of their strategic
• 49:29thinking around oncology,
• 49:31maybe just share you know with the
• 49:34panelist as well as the audience.
• 49:36You know how will is thinking about
• 49:39their oncologist strategy and what
• 49:40might be similar in in regards to
• 49:42Lillie with other major companies.
• 49:44But also, you know what might be different,
• 49:47you know,
• 49:48sort of with a focus on where
• 49:50you see the ball moving and
• 49:52back to sort of Craig's opening,
• 49:54comments are really trying to
• 49:56give people an understanding of
• 49:58what the big oncology franchises
• 50:00are going to be looking for.
• 50:02You know five and 10 years down the
• 50:04road when investigators work starts.
• 50:06Starts coming online.
• 50:09Yeah, I mean big formal environments
• 50:12are complicated places.
• 50:14I think they're they're confusing
• 50:16from the outside to try to interpret
• 50:19that were confusing to me when I
• 50:21was working at a small company,
• 50:23and they must be confusing to many of you.
• 50:26Is sometime collaborators,
• 50:27and I think there's like three
• 50:29or two or three reasons for that.
• 50:32One reason is large farmers are
• 50:34constructed and what they'll call most
• 50:36of them as a matrixed organization.
• 50:38So that means there are these
• 50:40technical disciplines that are
• 50:41somewhat independent of each other.
• 50:43So the commercial group.
• 50:45Is the commercial group the
• 50:46Biology discovery group?
• 50:47Is the biology discovery of the
• 50:49pharmaceutics people are their own group?
• 50:51The business development or their
• 50:53own group and they might report
• 50:55up into common structures,
• 50:56but if you as an outsider or
• 50:59interacting with somebody,
• 51:00it's really hard to from their business card.
• 51:02Sort of know what political entity
• 51:04they represent in the larger company,
• 51:06so you may think that you have
• 51:08the ear of a company or not,
• 51:11but it's really hard to know
• 51:13what political sort of dynamics
• 51:14are going on behind the scenes.
• 51:16That may or may not allow that person
• 51:19to deliver on what you're talking about
• 51:22or delivering the way you'd hope,
• 51:24and so one of the things I've tried to do it.
• 51:28Lily is break that down as much as
• 51:31possible and make our portfolio is
• 51:33coherent as possible all the way
• 51:35from target ID to first approval
• 51:37and not have these gating technical
• 51:40go no goes where at any moment the
• 51:43rug could be pulled out and that's
• 51:45the problem with the matrix model.
• 51:47Is that they often can lead to
• 51:51incoherent decision making, I think.
• 51:53A second so I,
• 51:55I think two other themes worth
• 51:57mentioning is the commercial
• 51:59entities at these companies.
• 52:00The ones who are marketing
• 52:02approved products have a lot
• 52:05of say on what happens in R&D.
• 52:07They have this idea of what moves
• 52:10the needle and they still see
• 52:12the world through the lens of
• 52:15conventionally defined markets.
• 52:17Lung cancer is bigger than you know,
• 52:19Melanoma and Melanoma is bigger
• 52:21than you know.
• 52:22Neuroendocrine tumors anurans
• 52:23bigger than some even rare orphan,
• 52:25so they're going to see the
• 52:27world commercially an like.
• 52:29They'll use this like troubling phrase.
• 52:31You know what moves the needle?
• 52:33Can we make a billion dollars
• 52:35on this drug a year?
• 52:37Can we make 5 billion dollars a year
• 52:40on this drug if it's just 200 million?
• 52:43We don't even want to hear about it,
• 52:46so there's this.
• 52:47In many large farmers,
• 52:48this disproportionate commercial
• 52:49voice that affects strategic thinking
• 52:51and that voice is not futuristic,
• 52:53it's backward looking at sort of water,
• 52:56the franchises that already exist
• 52:58and are proven.
• 52:59And can we can we Bolt on to those
• 53:02existing franchises in ways that
• 53:03sort of feel familiar so as to
• 53:06fill in holes from patent cliffs.
• 53:08And that's not,
• 53:09in my opinion the right way to
• 53:12look to the future, and then the third.
• 53:15I think in companies that have
• 53:17more R&D influence at the top.
• 53:19They are thinking about futuristic platforms.
• 53:22They are thinking about thematic
• 53:24bets that they feel they don't want
• 53:27to feel like they've missed out on.
• 53:30Things like gene therapy, self therapy.
• 53:33Or an AI crisper like big delivery,
• 53:36big idea, new modality, kind of thinking.
• 53:38And then there are a handful of companies
• 53:41that are willing to risk capital it
• 53:44just not missing fear of missing out.
• 53:46They're not going to quote over
• 53:49pay for that optionality.
• 53:50But in other words,
• 53:51in the absence of an approved product,
• 53:54but they'll place some bets and I
• 53:57think that's sort of 1/3 theme that
• 54:00I think can drive some collaboration.
• 54:03So
• 54:04can I just ask follow up questions?
• 54:07Josh, you say.
• 54:08Some companies have a greater appetite
• 54:10for that type of early platform.
• 54:13They don't want to miss out
• 54:16type of approach.
• 54:17What distinguishes those
• 54:18companies from their peers?
• 54:21Some of its corporate
• 54:23structure and an individual.
• 54:24The force of individual personality,
• 54:26which is the most surprising and
• 54:28Lee satisfies ING answer and give
• 54:30you so you know you've been in a
• 54:33complicated room of decision makers.
• 54:35There are some rooms that are dominated
• 54:38by certain voices that and those,
• 54:40and that's separate from their title.
• 54:42Sometimes an some others have
• 54:45org structures that represent
• 54:46that you know who's at the top is
• 54:49that is the CEO of the company.
• 54:51Does he come out of commercial or
• 54:53does he come out of research or she?
• 54:56It's a very what is the last
• 54:58board meeting they had and what
• 55:00pressures did the executive team
• 55:02feel coming out of that board?
• 55:05Meeting?
• 55:05Was the board feeling like
• 55:07cash poor and risk averse?
• 55:08Or was the where they fear
• 55:10of missing out because their
• 55:12competitor just did a big deal that
• 55:15they feel embarrassed that they
• 55:16didn't get to look at like these?
• 55:19Are these like incredibly soft,
• 55:21unknowable things?
• 55:21That that prevent me from really
• 55:24answering you in a in a coherent way.
• 55:26But you know, at you've been on
• 55:29the other side of the CEO of A
• 55:32of a smaller company that was now
• 55:35now you're on the other side.
• 55:38How can you as a CEO of a biotech
• 55:41position yourself so that you can take
• 55:43advantage of some of these unique
• 55:46characteristics of the marketplace?
• 55:49Can you create a market without
• 55:51losing the bird in the hand?
• 55:56What do you mean by
• 55:58burden when you're when you
• 56:00want to sell yourself right?
• 56:01If you get an Overture, how do you
• 56:04make sure that your company is is?
• 56:06What is the market value of your company?
• 56:09If you only have one interested party?
• 56:14Well, if you look at like
• 56:16Form 14 SEC documents that
• 56:18describe the anatomy of most
• 56:19M and a deals 70% of them are
• 56:22one party deals, there's all.
• 56:24There's not a competitive process.
• 56:26So that's just that's just how it goes.
• 56:28The majority of the time there's
• 56:30only one party at the table.
• 56:32The second assumption I always
• 56:34make is every company that's pre
• 56:36commercial is for sale at all times.
• 56:39So like the notion that like there's this
• 56:42board of Directors or investor base,
• 56:44that's hoping that's holding out, you know,
• 56:47most credible offers are considered,
• 56:49and it usually taken,
• 56:51so I don't really see this sort of
• 56:54waiting for perfection mentality.
• 56:56Everybody's for sale.
• 56:57If you're a public company,
• 56:59your prices listed on the ticker
• 57:02everyday there's some takeover premium
• 57:04that needs to be added to that.
• 57:06Whether that's a 20% premium or 100% premium.
• 57:09Is sort of up to the multiparty
• 57:13dynamic that you alluded to earlier,
• 57:16or the swagger of your banker
• 57:19and your CEO or just the lacquer?
• 57:23Black of discipline or intense
• 57:24discipline of the counterparty?
• 57:26I mean, I can't.
• 57:27These are incredibly like human
• 57:29one off moments in time,
• 57:31like there's again no strategic way
• 57:33that I can give you first order advice.
• 57:36Just spin my Tim.
• 57:38What have you seen is as a board
• 57:41member in this.
• 57:42And I agree, I think. First of all,
• 57:46most most lemonades are one party,
• 57:49and as you know, so the notion of this
• 57:52competitive processes is not the norm,
• 57:54it's it's usually the exception.
• 57:56But I do think I do think most boards
• 57:59have to be open to respectable offers.
• 58:02You know 'cause boards are representing
• 58:04the interests of shareholders,
• 58:06so I'm going to have a
• 58:08responsibility to entertain any.
• 58:10Any offer behalf of investors.
• 58:12I think it's it's all fair game I guess.
• 58:15Just one follow up with Josh.
• 58:18So like what would be your advice too?
• 58:21You know the panelists here,
• 58:23or an academic sitting
• 58:25in the audience if they,
• 58:27if they wanted to really check for real
• 58:30interest in their technology within a
• 58:32big pharma company, what would you say?
• 58:36Is that the key?
• 58:38To making sure that whatever that
• 58:40interaction is will give a person
• 58:42quality feedback is is there a way
• 58:44to get that or is it you think
• 58:46it's a little bit of a hit or
• 58:48miss in a large farm environment?
• 58:50Yeah,
• 58:50and then let's do large farm
• 58:52and then go down to you know
• 58:54how biotech might be different?
• 58:56It's
• 58:57it's important to have a champion in in R&D.
• 59:01Who has influence in?
• 59:03In the company and can drive to
• 59:06a deal and I think it's always
• 59:09best to have R&D level champions.
• 59:12I mean there are other sources of
• 59:14capital and large farmers like
• 59:15a lot of them have some kind of
• 59:18sort of internal venture fund,
• 59:19or they'll make strategic passive
• 59:21investments that sort of without
• 59:23real buy in from R&D sometimes,
• 59:24or like token by in so I think those
• 59:27are usually the two parties that most.
• 59:30Small companies interact with either
• 59:32the you know the the VC group
• 59:35within the company or the R&D.
• 59:37I think if you're in a series
• 59:39of meetings where the seniority
• 59:41of the attendees is not going up
• 59:43or staying the same,
• 59:45you're not seeing things in writing.
• 59:48You don't feel like you're on a
• 59:50timeline like the diligence field
• 59:52goal post keeps shifting around
• 59:54on like what the next steps are.
• 59:56I think those are all subtle clues that
• 59:59it's kind of going sideways and then,
• 01:00:01on the other hand,
• 01:00:03if you really seeing like a focused
• 01:00:05effort to get something done and
• 01:00:07you're seeing consistency of voice,
• 01:00:09not just in your conversation,
• 01:00:11but with Yale Tech Transfer,
• 01:00:13that's an encouraging sign.
• 01:00:16Great, thanks.
• 01:00:16So we're going to shift some
• 01:00:19questions from the audience. Again.
• 01:00:21Just remind the audience that again,
• 01:00:23we've disabled the chat room,
• 01:00:25so if you want to ask a question,
• 01:00:28raise your hand and then the people
• 01:00:31supporting the logistics will engage with
• 01:00:33you and will get your question answered.
• 01:00:36Irmo Glaser has a question.
• 01:00:39Asked if you can open the mic.
• 01:00:49And yet Go ahead your mikes,
• 01:00:54open anything. No, not yet. Gamma,
• 01:00:57it looks like your Mike still baby muted.
• 01:01:07OK, try now. Thank you very much.
• 01:01:11I like to. No. Whether
• 01:01:16there are guidelines, I
• 01:01:18am like a an investor.
• 01:01:20Just looking around if
• 01:01:22there are guidelines as to. How
• 01:01:27do they? The pitch people.
• 01:01:32Speech to investors to make sure that
• 01:01:36all the basic Yale ethical considerations
• 01:01:39are in place.
• 01:01:41In other words, how
• 01:01:43do we know
• 01:01:44that the information they are
• 01:01:47giving us 100%?
• 01:01:49Size base are not. Dangit by the the
• 01:01:55interest in getting funding. To be very
• 01:01:59blunt, great yeah, thanks for the question.
• 01:02:02Thinking jump useless to you around.
• 01:02:05Maybe you can speak a little bit about sort
• 01:02:09of the venues use for this purposes as well
• 01:02:13as sort of the curation of what goes in.
• 01:02:17Sure, thanks Tim. So gramma.
• 01:02:20Thanks for your question.
• 01:02:21So when we have faculty pitching
• 01:02:24to investors or two companies,
• 01:02:26they're generally working very closely with.
• 01:02:29The with OCR with my colleagues
• 01:02:31here in the Tech Transfer Office.
• 01:02:33So for example I had mentioned earlier
• 01:02:36in the chat that there's a pitch
• 01:02:38fest being held in earlier December.
• 01:02:40These are the applicants for our
• 01:02:42Blavatnik Fund for Innovation Awards,
• 01:02:44so these faculty I think there's
• 01:02:46about 30 of them this year.
• 01:02:48Have all applied for this award.
• 01:02:50They're giving 5 minute pitches
• 01:02:52in their coached extensively,
• 01:02:53not only by people in the
• 01:02:55tech transfer office,
• 01:02:56but also by a board of
• 01:02:58reviewers which includes.
• 01:03:00Investors and also people from
• 01:03:02corporate VC funds as well as
• 01:03:04people in the pharma and biotech
• 01:03:07community are entrepreneur in
• 01:03:09residence network and you know,
• 01:03:11I think we all expect that Yale faculty
• 01:03:14are going to adhere to the highest
• 01:03:17standards of scientific integrity
• 01:03:19when there's any kind of conflict of
• 01:03:22interest management plan in place,
• 01:03:24faculty are expected to make those
• 01:03:27those financial interests known
• 01:03:29publicly when in publications or.
• 01:03:31Nations or the like.
• 01:03:32So I hope that answers your question.
• 01:03:37Thanks John. I think there's been a
• 01:03:40couple mentions of the Botnick program
• 01:03:42I think runs you had it in the slides.
• 01:03:46I think some of the panels
• 01:03:48have been involved in this.
• 01:03:49I think John you just mentioned, maybe John.
• 01:03:52I don't know if you'd be best
• 01:03:54or even Ranji just to speak a
• 01:03:56little bit about that program.
• 01:03:58'cause again I think it's one of the
• 01:04:00key parts of the infrastructure here.
• 01:04:02Trying to help sure bridge
• 01:04:04academia into commercialization.
• 01:04:05Yeah, I can give a little bit of an overview,
• 01:04:10so yells been very lucky and we're
• 01:04:13very grateful to have a generous award
• 01:04:16from the Bubonic Family Foundation.
• 01:04:18This is an award or foundation set up
• 01:04:22by Lindblad Botnek and similar awards
• 01:04:25been made to Harvard into Columbia,
• 01:04:28so yells received a total of,
• 01:04:30I think, $25,000,000 from the
• 01:04:33Bubonic Family Foundation.
• 01:04:34And this is used to.
• 01:04:36Fund projects at Yale that have
• 01:04:39significant potential to have an
• 01:04:41impact on human health and medicine.
• 01:04:43And every year we have a contest amongst
• 01:04:46faculty at Yale who apply for these
• 01:04:49awards there between 100 and $300,000,
• 01:04:52and generally these are quite competitive.
• 01:04:55I would say there are significantly more
• 01:04:58competitive than I jar one award for example,
• 01:05:01and some of these have already
• 01:05:03advanced to the point of having
• 01:05:05significant venture capital investment.
• 01:05:08So for example, city.
• 01:05:09Had launched a company last
• 01:05:11year called Evolved Immune,
• 01:05:12which raised I think something like
• 01:05:1435 or $36,000,000 in and arround,
• 01:05:17and this was based on research
• 01:05:18that was in part funded by the
• 01:05:21Bubonic Award and Ranjit.
• 01:05:22I know you've applied for
• 01:05:24the award this year,
• 01:05:26you could talk perhaps a little
• 01:05:28bit about your experience or
• 01:05:29city talk about your experience
• 01:05:31and in going through the process
• 01:05:33perhaps they are happy to know.
• 01:05:35See
• 01:05:36if you want to go first or
• 01:05:38some not dominate discussion.
• 01:05:39Oh sure, I think the bubonic.
• 01:05:43Our process is extremely rigorous.
• 01:05:45We went through multiple rounds of
• 01:05:49training and multiple rounds of.
• 01:05:52Discussion internally first,
• 01:05:53fully badly the signs and then extensive
• 01:05:57discussion with the other partners.
• 01:06:00And we are fortunate to be funded based
• 01:06:03on the science by the panel of extensive
• 01:06:08community from multiple entities,
• 01:06:11including academic industry venture.
• 01:06:13And then we're able to advance
• 01:06:16science because of the award,
• 01:06:18and then eventually able
• 01:06:20to create a startup so.
• 01:06:23Yeah, yeah I'll
• 01:06:24just. I mean,
• 01:06:25I've absolutely loved the process.
• 01:06:26You know, we started a company called
• 01:06:29Cyber Exca Therapeutics a few years back,
• 01:06:31and that was not through this process
• 01:06:33and I was able to sort of compare
• 01:06:35contrast and the process for Athena,
• 01:06:37which was recently awarded
• 01:06:38above that Nick Grant,
• 01:06:39and we're in the middle of the award.
• 01:06:42I can tell you is it was a
• 01:06:44phenomenal learning experience.
• 01:06:45You know each round of the pitch is not
• 01:06:48only learn how to refine your pitch,
• 01:06:50but also from the VC folks on
• 01:06:52some of these calls would sort of
• 01:06:54give a lot of real time feedback.
• 01:06:57And you know,
• 01:06:57I I kind of think of it as a rapid
• 01:07:00acting SP IR that's internal
• 01:07:02to the Yelp Community.
• 01:07:03And so I think it's a great opportunity.
• 01:07:06It allows you to do a little bit of the
• 01:07:08risking still inside the walls of Yale.
• 01:07:11Before that, you know,
• 01:07:12startup really takes off into the air.
• 01:07:14So yeah,
• 01:07:15really a big fan.
• 01:07:17Yeah yeah, I'll just add from
• 01:07:19being part of some of those
• 01:07:21values for those in the audience.
• 01:07:23Maybe not as familiar
• 01:07:24with the ecosystem here.
• 01:07:26You know there there are multiple venues,
• 01:07:28whether it's provodnik pitch and
• 01:07:30even you know precursors of those.
• 01:07:33Where you know vetting goes on by, you know,
• 01:07:38people who you know been there before,
• 01:07:41including scientists, venture capital,
• 01:07:43people who really pressure test
• 01:07:45opportunities. So again,
• 01:07:47I think there's been a nice build,
• 01:07:50an infrastructure around Yale really to
• 01:07:53support that growth and mentoring of
• 01:07:55scientists interested in translating
• 01:07:58their research to commercialization.
• 01:08:00And the quality is high because
• 01:08:03of those interactions.
• 01:08:04I do have a couple questions
• 01:08:06from the audience that were.
• 01:08:08Questions that that came in in advance.
• 01:08:11Let me put the first one out there.
• 01:08:14Maybe maybe.
• 01:08:15Ranjit and Josh just thinking
• 01:08:18about the nature of this question
• 01:08:21it might be addressed by you.
• 01:08:24The question is,
• 01:08:25are rare tumors disadvantaged?
• 01:08:27You know,
• 01:08:28and sort of this translation from
• 01:08:30from science to commercialization,
• 01:08:32and this is someone who's
• 01:08:34interested in units,
• 01:08:36primitive neuroactive dermal tumors.
• 01:08:37So how did Reggie I know?
• 01:08:40You have some interest in these areas?
• 01:08:43And Josh,
• 01:08:44I know you've had certain experience in and
• 01:08:47what might have been considered rare cancers.
• 01:08:50Maybe if you guys can just
• 01:08:53adjust that. Start 'cause I've
• 01:08:54learned so much from Josh and
• 01:08:56my time that I've known him and.
• 01:08:59Yeah, so the first drug I developed at
• 01:09:04box Oncology with was a TRK inhibitor.
• 01:09:08For a population that in the United States
• 01:09:10was probably about 2500 patients a year,
• 01:09:13assuming you could find every last one
• 01:09:15which you certainly couldn't because of the
• 01:09:18state of the diagnostic testing environment.
• 01:09:20So, like I candidly, I think Big Pharma
• 01:09:22is not seeking out those opportunities
• 01:09:25until there's an approved product.
• 01:09:28And then there's just so few.
• 01:09:30There's just so little in the cupboards
• 01:09:33of approved products that they can
• 01:09:36add to their commercial pipeline.
• 01:09:38They get interested after approval
• 01:09:40when they can begin to think about
• 01:09:43pricing and think about time on
• 01:09:45drug and prevalence modeling,
• 01:09:47and maybe they dare to dream once it's.
• 01:09:51It's FDA approved,
• 01:09:52but they almost never green light.
• 01:09:54An interim being,
• 01:09:55like really reductive here,
• 01:09:57and I'm not talking about my own company,
• 01:09:59which now I have some
• 01:10:01influence on their thinking,
• 01:10:02but I think I think most want to see
• 01:10:05that the commercial guys nip that in the
• 01:10:08Bud at a lot of large companies early.
• 01:10:11Let's just say,
• 01:10:12I think in contrast,
• 01:10:13Wall Street gives a lot of value
• 01:10:15to the rare company.
• 01:10:17The Wall Street places a premium
• 01:10:19on unlikelihood of success,
• 01:10:20and that's I think why rare tumors are
• 01:10:22exciting and that presumably there.
• 01:10:24Their mechanistically better understood,
• 01:10:26certain maybe more homogeneous
• 01:10:28in their in their their biologic
• 01:10:30drivers and therefore druggable with
• 01:10:32a higher probability of success,
• 01:10:34and so I always probable eyes success over.
• 01:10:37I always value PTS probability technical
• 01:10:39success over commercial potential,
• 01:10:41and I'm weird that way,
• 01:10:43but I think I think Wall Street.
• 01:10:46I think Wall Street gets it,
• 01:10:48they just want to see great data.
• 01:10:51They want to understand.
• 01:10:53Is this a company?
• 01:10:55That's going to be worth greater than
• 01:10:57zero on their leader programs or not.
• 01:11:00An being in a group of programs that
• 01:11:02is on the way to an FDA approval or
• 01:11:05not is a big fork in the road for the
• 01:11:09biotech investing universe out there.
• 01:11:11And small small companies.
• 01:11:13So like you know,
• 01:11:14there's companies out there company
• 01:11:16out there developing amenan inhibitor
• 01:11:18for mixed lineages, leukemia.
• 01:11:19You know,
• 01:11:20there's two companies out there doing it
• 01:11:23an they're able to attract capital and.
• 01:11:25In a following and people are
• 01:11:27excited about being exposed to that.
• 01:11:29That's not a kind of program you'll
• 01:11:31run across in most large pharmas,
• 01:11:34though.
• 01:11:36Yeah,
• 01:11:36and and I'll add, you know,
• 01:11:38as a sort of on the clinical side,
• 01:11:40there's really now and infrastructure
• 01:11:42that's allowing a lot of these rare tumor
• 01:11:44trials to progress much faster. As you know,
• 01:11:47adult pediatric brain tumor doctor.
• 01:11:48We've been working on things
• 01:11:50like IDH mean gliomas in kids,
• 01:11:52which is actually not that common,
• 01:11:54and we now have pretty robust cooperative
• 01:11:56groups that are ready to jump on,
• 01:11:58sort of precision medicine angle.
• 01:12:00Another interesting thing is a lot of
• 01:12:02these foundations are becoming more active.
• 01:12:04The National Brain Tumor Society,
• 01:12:06for instance, is started a venture fund.
• 01:12:08To try to get the more rare
• 01:12:10tumors funded kidney cancer,
• 01:12:11we look at FH Mutant HL RCC.
• 01:12:13This is like 300 cases a year,
• 01:12:16but there's actually now a whole group
• 01:12:18that's trying to fund these smaller trials,
• 01:12:20and then when you throw that together with
• 01:12:22the orphan status priority review vouchers.
• 01:12:24Depending on which which area are
• 01:12:26looking at that there there are pieces
• 01:12:29of the puzzle that are coming together
• 01:12:31that are making this a little bit
• 01:12:33more tractable.
• 01:12:34I think the existential risk
• 01:12:35of everything we just said
• 01:12:37is the drug pricing debate.
• 01:12:38So if if if you example say.
• 01:12:42If we can accept that there is such
• 01:12:45a thing as a $20,000 per month
• 01:12:47or $30,000 per month therapy,
• 01:12:49then we create legislation or mandates
• 01:12:51around price caps and limits.
• 01:12:53I I don't know how the financial model
• 01:12:56works even at the small company level,
• 01:12:58and I'm not seeing enough nuances
• 01:13:00in the public policy debate that's
• 01:13:02really tackling that question.
• 01:13:05Yep.
• 01:13:08Yeah, you still let you look
• 01:13:09at and I would just add.
• 01:13:12You know so so small tumors are great.
• 01:13:15If you really understand the biology,
• 01:13:17'cause the therapies can
• 01:13:19have a tremendous impact.
• 01:13:21I mean, Josh response rates with your
• 01:13:24product's were in the range of 50 sixty, 70%.
• 01:13:27Just remind us 80 percent, 80%.
• 01:13:29And that's not only unheard of in cancer.
• 01:13:33That's unheard of.
• 01:13:34Almost any indication across the industry.
• 01:13:36So when when you have something
• 01:13:39so profoundly impactful,
• 01:13:40you know, just because of the.
• 01:13:43Transformative benefit that
• 01:13:44has to patient that that really
• 01:13:47subscribe value so you know a small
• 01:13:50population with a really potent
• 01:13:52therapy rightfully can be can be
• 01:13:55valued highly and therefore draw,
• 01:13:57certainly,
• 01:13:57do investment is just want enough
• 01:14:00from investors from the small
• 01:14:02biotech community.
• 01:14:03So I will add that there's a way to
• 01:14:05have a strategy where your first solid
• 01:14:07tumor phase one might have all comers
• 01:14:09and you have a dream that your your
• 01:14:12follow on trial is for that population.
• 01:14:14Obviously that's always difficult to
• 01:14:15walk that line, but if there is a way,
• 01:14:18certainly many companies have done it.
• 01:14:19Then you can kind of hedge your
• 01:14:21bets a little bit, but. But
• 01:14:25it still takes an enormous amount of
• 01:14:28capital to develop a rare tumor drug.
• 01:14:30Yeah, our second drug was a.
• 01:14:33You know, targeting 2% of the lung cancer
• 01:14:36community with red alterations and.
• 01:14:38Anne medullary thyroid cancer.
• 01:14:40We were running GNP manufacturing
• 01:14:42campaigns that cost 3040 million dollars.
• 01:14:45Just the manufacturing and then you throw
• 01:14:48on top of that like it takes hundreds of
• 01:14:52millions of dollars to get a drug approved.
• 01:14:55No matter what the market potential is,
• 01:14:58it's just there's these fixed
• 01:15:01costs of compliance, manufacturing,
• 01:15:02pre clinical data management,
• 01:15:04post safety, post marketing,
• 01:15:06safety monitoring like there's just.
• 01:15:09The small product in the big product
• 01:15:10are exposed to the same fixed cost.
• 01:15:12You know issues.
• 01:15:13And so don't assume you can skunk work
• 01:15:16it forever if the drug starts to work,
• 01:15:19you're going to real capital in a
• 01:15:21real management team behind it.
• 01:15:25Yep. Um? So again, open up to
• 01:15:29the audience for any questions,
• 01:15:32raise your hand and we'll get
• 01:15:34you into the meeting and Kathy,
• 01:15:36you make me aware of any
• 01:15:38of those that I'm missing.
• 01:15:40Let me it just make an observation and then
• 01:15:43you know pass on a question to the panel.
• 01:15:47So one thing that I'm struck by
• 01:15:50about Yale compared to other.
• 01:15:52Institutions with worldwide were now
• 01:15:56is that while you know there's an
• 01:16:00incredible depth of talent and science.
• 01:16:05You know around every corner.
• 01:16:07The institution has a smallness to it in
• 01:16:10terms of being able to interact with it,
• 01:16:13which to me is like really unique
• 01:16:16compared to other places I go,
• 01:16:18and I think it's it's A wonderful attribute.
• 01:16:21I see that also in the collaborations
• 01:16:24within Yale.
• 01:16:25So again, I know many of you and I
• 01:16:27see a lot of collaborations going on.
• 01:16:30You know, with within,
• 01:16:31within the walls of Yale,
• 01:16:33and within that the Cancer Center run sheet.
• 01:16:35I think you called some of this out.
• 01:16:38Army Reserve without the lab to the clinic.
• 01:16:41Maybe if you could speak a little bit more
• 01:16:44about that as sort of my angle is you know,
• 01:16:47you know translation is so
• 01:16:49important and markers of translation
• 01:16:50or so important in Ranji.
• 01:16:52You talked about this iteration of
• 01:16:54Lab to the clinic and the importance
• 01:16:56of tissue human tissue tested with
• 01:16:58your drug and interrogating that.
• 01:17:00Understand what's going on.
• 01:17:01So maybe lunch.
• 01:17:02It'll throw it to you,
• 01:17:04but I really would ask others
• 01:17:05really just to talk a little bit
• 01:17:08about some of their collaborations.
• 01:17:10Within the walls,
• 01:17:11email that they think are really
• 01:17:12unique and really haven't enabled.
• 01:17:14You know you to do what you want
• 01:17:17to do. Question and you know, as I mentioned,
• 01:17:19a bit yellow while I was a resident at
• 01:17:22Sloan Kettering for about five years
• 01:17:24and was able to compare experiences
• 01:17:26that at much larger sort of complexes.
• 01:17:28And one of the reasons I came back
• 01:17:30to you was that that spirit at the
• 01:17:32Cancer Center and on the campus.
• 01:17:34It's a very small close knit community,
• 01:17:36but with very, very big ideas and deep
• 01:17:39collaborations and certainly doctor
• 01:17:40fuses really engender that further at
• 01:17:42the center and it's just a wonderful
• 01:17:44place to be and just an example is,
• 01:17:46you know when we found that
• 01:17:48you know I DH mutations.
• 01:17:49Cause PARP inhibitor sensitivity and
• 01:17:50it was sort of the opposite of the
• 01:17:52current approach in the clinic to use
• 01:17:54I DH inhibitors that suppress the mutation.
• 01:17:56We actually say we should exploit the defect.
• 01:17:58We still need to figure out if it's got legs
• 01:18:01in the clinic and that's what we're doing,
• 01:18:03but it was the folks like Pat Larusso,
• 01:18:05Inpo leader, who run Phase one here at Yale,
• 01:18:07and, you know,
• 01:18:08we literally shoot down the Hall.
• 01:18:10You know,
• 01:18:10right when we're getting the paper ready?
• 01:18:12Brought the galley proofs over
• 01:18:13there and I said, well, you know,
• 01:18:15what do you think can we?
• 01:18:17Can we take a lap ribbon?
• 01:18:18Just run a trial?
• 01:18:19And just get this going her in Polydor.
• 01:18:22We sat down and had a Cup of coffee
• 01:18:24and we mapped it out and part of the
• 01:18:26reason it was so successful was that
• 01:18:28it isn't an assembly line type of
• 01:18:31approach and it gets back to Josh's
• 01:18:32comments of at the upper level of
• 01:18:34those people know the deeper science.
• 01:18:36Same thing here.
• 01:18:37If the clinical trials have a
• 01:18:39deep understanding and respect and
• 01:18:40relationship with the science,
• 01:18:41you can have conversations with
• 01:18:43pure basic scientist anyone and
• 01:18:44really integrate that data.
• 01:18:45And so when patent Jeff and I and
• 01:18:47Peter Glaser folks are mapping those
• 01:18:49trials that we're thinking about.
• 01:18:50The on treatment biopsies the PK,
• 01:18:52PD biomarkers and and we're getting
• 01:18:54deep in the science and you know
• 01:18:56Pat as a deep respect for it and
• 01:18:58we kind of go back and forth and no
• 01:18:59ones making assumptions about you
• 01:19:01know the other part of the coin.
• 01:19:02The trial design versus the science,
• 01:19:04and so I'll leave it that.
• 01:19:05But that's just one example of why
• 01:19:07I think things have flourished here.
• 01:19:10I also just add my experience
• 01:19:13with the Yale Cancer Center.
• 01:19:15I'm actually in on the main campus,
• 01:19:19so I teach undergraduates biology.
• 01:19:21So for me the Yale Cancer Center
• 01:19:24has been instrumental in making sure
• 01:19:27that I know what's going on from a.
• 01:19:30From a clinical point of view,
• 01:19:33that the retreats the seminar series.
• 01:19:36The pilot grants that are available to
• 01:19:39faculty to facilitate collaborations among.
• 01:19:41People from different disciplines
• 01:19:44really make for a very tightly
• 01:19:48dense collaborative network.
• 01:19:51But I just wanted, you know,
• 01:19:53put put this 2 two finer points on this
• 01:19:56with respect to my to recent companies.
• 01:19:59When I had this a bit of a crazy
• 01:20:02idea of how to degrade proteins
• 01:20:05an I was thinking about how to.
• 01:20:08Start this company are Venice.
• 01:20:10I knew that I needed to have
• 01:20:12a killer app right?
• 01:20:14And so the beauty of the platform technology.
• 01:20:17It could be applied to
• 01:20:19many different targets.
• 01:20:20And so I sat down with Dan Pitch Black.
• 01:20:25A prostate cancer specialist
• 01:20:27here and with my investor an.
• 01:20:30It was really nice to be able to sit and
• 01:20:34have the investor listen to the end user.
• 01:20:38If you will hear what could be a
• 01:20:41unique application of this technology
• 01:20:44and and I think that that really
• 01:20:47helped me seal the deal in terms of
• 01:20:50getting our business off the ground.
• 01:20:53More recently another platform technology
• 01:20:55company we were thinking about indications.
• 01:20:58I was able to go to the leadership
• 01:21:01of the Cancer Center and say,
• 01:21:03listen,
• 01:21:04would it be possible for me to
• 01:21:06get together three or four basic
• 01:21:09researchers and cancer in this
• 01:21:11area and just to have a sit down?
• 01:21:13Or we could throw out ideas and really
• 01:21:16whiteboard things and really allowed
• 01:21:18for this nascent company to be able
• 01:21:21to have again real world interactions.
• 01:21:23And so it makes for a I think a
• 01:21:26very unique place here at you.
• 01:21:31Fair City, any any comments?
• 01:21:33You know in regard to, you know,
• 01:21:36some of your collaborative experiences. Sure,
• 01:21:39I think your Cancer Center.
• 01:21:41It's a wonderful place in I have so many
• 01:21:45different experts experts in collectively.
• 01:21:48We basically cover the entire
• 01:21:50cancer expertise in this place
• 01:21:53and you can basically find the.
• 01:21:56Conditions and basic scientists in.
• 01:21:59Physician scientists across
• 01:22:01the board and no matter what
• 01:22:03cancer type you trying to?
• 01:22:05Only in order to discuss with.
• 01:22:08Really, truly collaborative
• 01:22:09environment over here.
• 01:22:13In, say, anything that so I would second
• 01:22:16all that has been said before,
• 01:22:18and I think one of the things that
• 01:22:21we've been primarily interested in
• 01:22:23is we know that our strategy can be
• 01:22:26used to treat drug resistance and the
• 01:22:29opportunity to get patient samples
• 01:22:31so that we can make patient derived
• 01:22:33xenograft models has been really
• 01:22:36instrumental for us to kind of see
• 01:22:38whether or not we have functional
• 01:22:41activity in drug resistant tumors.
• 01:22:44That's great, thanks birthday.
• 01:22:46So we do have a question from
• 01:22:50the audience. Alexander Let's
• 01:22:53see if we can get you activated.
• 01:22:56Yeah, hi. Can
• 01:22:57anyone hear me?
• 01:22:58Yeah we can hear.
• 01:23:01OK, thank you.
• 01:23:02Thank you everybody for coming together.
• 01:23:05It's been really, really exciting.
• 01:23:06So my question is open anyone on the panel?
• 01:23:10I'm just curious about the broad
• 01:23:12cultural differences between
• 01:23:13industry and academia specifically.
• 01:23:15Do you ever have or see very successful
• 01:23:18academic scientists and clinicians who,
• 01:23:20for personality reasons experience
• 01:23:21a lot of friction in their
• 01:23:24involvement with industry?
• 01:23:25And Conversely,
• 01:23:25what kinds of personality traits do
• 01:23:28you think predict maybe a smoother
• 01:23:30transition from academia to industry?
• 01:23:33Well, open that up. I love the question.
• 01:23:41Thank you for it.
• 01:23:43I think about it all the time.
• 01:23:46I think a big one of the biggest differences.
• 01:23:51Is the mindset around risk taking?
• 01:23:58In academia, it's OK to like place a lot
• 01:24:01of bets and be wrong most of the time.
• 01:24:04Learn some interesting things along the way.
• 01:24:07Get some publications,
• 01:24:08even if you're wrong.
• 01:24:10I'm referring to even like clinical
• 01:24:12publications, posters that said.
• 01:24:13An industry you're accumulating a track
• 01:24:16record always the things that you,
• 01:24:18the projects that you launch
• 01:24:20and work on have to work.
• 01:24:23You need to see patient results and you
• 01:24:25can't just take Flyers all the time.
• 01:24:27It's kind of like being a
• 01:24:29movie producer in Hollywood.
• 01:24:30Like if you the last movie you make
• 01:24:32if nobody comes with the box office,
• 01:24:34you don't get to make another movie.
• 01:24:36Not saying it says I don't think
• 01:24:38it says reductive is that quite?
• 01:24:40I mean this we have a high
• 01:24:42failure rate in this business,
• 01:24:44but if you're just somebody who places bets
• 01:24:46because it's someone elses money and like.
• 01:24:48There's a very common academic behavior of,
• 01:24:51like, you know, I'm just.
• 01:24:53It's not my money.
• 01:24:54I'll learn some science.
• 01:24:56It's an option.
• 01:24:57Benefit goes well.
• 01:24:58In the upside,
• 01:24:59if it's on the downside,
• 01:25:00who cares?
• 01:25:01I'll move on to the next thing
• 01:25:03like that's a very I'll just say
• 01:25:05that's a more academic mindset,
• 01:25:07and the more industry mindset is like no,
• 01:25:09this I'm bringing all my best relationships
• 01:25:12and credibility to bear on this one project.
• 01:25:14Better, better work,
• 01:25:15better work and patience.
• 01:25:17Better ultimately,
• 01:25:17hopefully become an approved
• 01:25:19product that turns into a marketed
• 01:25:21medicine for patients like that,
• 01:25:22shift in mind is like.
• 01:25:24Very stark and I see a lot of folks
• 01:25:26who come in industry sort of mid
• 01:25:29and late career from academia,
• 01:25:31and they think that they'll come
• 01:25:33in be sort of a non high voice
• 01:25:36of logic and science and reason.
• 01:25:38The resident expert and be sort of
• 01:25:40off the hook on the harder parts of
• 01:25:43being right and on the harder parts of
• 01:25:46actually executing against the plan.
• 01:25:48And those folks don't do as well either,
• 01:25:51so I think both on like being
• 01:25:53right about your convictions.
• 01:25:55As well as being a contributor to
• 01:25:57the execution against the plan,
• 01:25:58those are the two behaviors
• 01:26:00that define success in industry,
• 01:26:02where in academia there needs
• 01:26:03to be room for failure.
• 01:26:05There needs to be room for exploration
• 01:26:07in multiple ideas and moving on
• 01:26:09to the next project to keep the
• 01:26:11academic mission moving forward.
• 01:26:12And I'm not judging one or the other,
• 01:26:15but they're they're not
• 01:26:16interchangeable in terms of behavior.
• 01:26:24Thanks Josh, anyone from the
• 01:26:27panel. Make a comma. Yeah,
• 01:26:30I'll just add 'cause I know
• 01:26:32we're running out of time,
• 01:26:33but you know in in recent years
• 01:26:35I I feel like I'm learning.
• 01:26:37Sometimes the friction 'cause we all.
• 01:26:39I think we've seen it I personally,
• 01:26:41but derive some sort of maybe
• 01:26:42insecurity on what we think. We know.
• 01:26:44What we don't know and this is
• 01:26:46really everyone involved in the drug
• 01:26:47development and I think very important
• 01:26:49principle is that from the process of
• 01:26:51just the molecule to getting it into
• 01:26:53a patient to then caring for that
• 01:26:55patient for several years afterwards.
• 01:26:57Every step of that process
• 01:26:58is enormously complex,
• 01:26:59and I thought I knew.
• 01:27:00A lot is an MD PhD work in
• 01:27:02the lab and in the clinic,
• 01:27:04and with Brexit going in
• 01:27:05the clinic this spring,
• 01:27:07you know unbelievably newfound
• 01:27:08respect for how difficult it
• 01:27:10is to get a drug just into the
• 01:27:11Ind and into a clinical trial.
• 01:27:13So I think really understanding
• 01:27:15and mutual respect often will
• 01:27:16stave off some of some of that
• 01:27:18friction in my opinion.
• 01:27:21Thanks Ron G. OK, so we are running
• 01:27:24up against the Clock here so again,
• 01:27:26thanks for the conversation.
• 01:27:28It's been great,
• 01:27:29sorry bout some of the disruptions,
• 01:27:31but hopefully you know we've been
• 01:27:33able to gather most questions.
• 01:27:35What I'd like to do right now
• 01:27:37is just turn the microphone over
• 01:27:39to Charlie Fuchs again just for
• 01:27:41a few closing remarks from him.
• 01:27:54Charlie please unmute.
• 01:27:56Sorry, sorry I want to thank him for
• 01:27:59running a phenomenal panel and all
• 01:28:01the panelists for great discussion.
• 01:28:03I think it was really instructive
• 01:28:06in terms of the science and frankly
• 01:28:08the challenges of what I think is
• 01:28:11at the forefront of cancer therapy.
• 01:28:13I also want to apologize to all panelists
• 01:28:16and the audience on the disruptions,
• 01:28:19and I can assure you that we are
• 01:28:21going to make sure that we don't
• 01:28:24experience a similar disruption.
• 01:28:26Again, I hope you all will use
• 01:28:28this as an opportunity to advance
• 01:28:30what was been a great conversation,
• 01:28:33because as I say,
• 01:28:34we want to build partnerships.
• 01:28:36I think you've heard today about the
• 01:28:38challenges of those partnerships
• 01:28:40and we want to make them smooth
• 01:28:42and successful because ultimately
• 01:28:44to really advance cancer therapy,
• 01:28:46it's going to require a community,
• 01:28:48so please feel free to reach out
• 01:28:50to me to the panelists.
• 01:28:52We hope this is the beginning
• 01:28:54of a conversation.
• 01:28:55In addition, I hope you'll all join us again.
• 01:28:58On Wednesday, December 9th,
• 01:29:00at 1:00 o'clock,
• 01:29:01when are third in the series of Yale engage,
• 01:29:04cancer will be defining mechanisms
• 01:29:06and biomarkers of sensitivity
• 01:29:08and resistance to anti cancer
• 01:29:10treatments and then finally,
• 01:29:11it just want to once again thank Tim.
• 01:29:14Tim is Tim Shannon is a member of the
• 01:29:17board of our Our Cancer Center and
• 01:29:19has been really a great supporter
• 01:29:22of all that we do and including
• 01:29:25running today's session and Tim,
• 01:29:26I'll turn it over you for
• 01:29:28the final closing remarks.
• 01:29:30Thanks
• 01:29:30Charlie, thanks very much.
• 01:29:32Again, yeah, so just let me extend thanks
• 01:29:34to the audience to our faculty panelists.
• 01:29:37Special thanks to Josh for carving out
• 01:29:39time of his day. Josh, we hope to.
• 01:29:42To see more and more here around Yale again,
• 01:29:45all I can say is you know,
• 01:29:48like most people on the call,
• 01:29:50this is my passion of trying
• 01:29:52to do hard things and.
• 01:29:54You know getting him into
• 01:29:56humans and hopefully making
• 01:29:57a difference in humans lives,
• 01:30:00so it's a great community to be part of.
• 01:30:04Yale's got great things going on.
• 01:30:06It is easy place to engage with so
• 01:30:09you know in reflection of the name of
• 01:30:13the event would encourage all of you.
• 01:30:16Again, we're interested to
• 01:30:17engage with Yale Cancer Center.
• 01:30:20Try to do some important things.
• 01:30:21No thanks everyone,
• 01:30:22and with that will sign off.