LifeSci Partners Podcast

Tune into Episode #2 of the LifeSci Search podcast with Andy Cronin (President & Co-Founder) and Ayesha Price (Sr. Director, Executive Search) as they host Iris Grossman (Chief Therapeutics Officer, Eleven Therapeutics) and Shahram Ebadollahi (Operating Partner, ARCHIMED & Former Chief Data Officer, Novartis) on the topic of AI and ML tools in Drug R&D. We get insights on how the tech is being leveraged in biotech and pharma along the R&D process, overall impact so far, thinking around AI and ML among leadership teams & boards, and perspectives on the competition for AI and ML talent within Life Sciences industry.

Tune into Episode #1 of the LifeSci Search Podcast.

In the clinical setting, the time it takes to address a serious problem can make the difference between life and death. To save as much time as possible, the necessary material – a vessel to do a coronary bypass, for example – needs to be readily available. However, due to the organic nature of that material, acquisition may take more time than you have, and the nature of the end-product may be suboptimal. Enter Humacyte. Using human-sourced cells, Humacyte creates Human Acellular Vessels (HAVs) that are non-immunogenic and available on demand. HAVs are in Phase 3 testing in the settings of both arteriovenous (AV) access, as needed for kidney dialysis, and trauma, as seen in severe injury, such as a war wounds. This indication has attracted the attention of the US Department of Defense and the Ukrainian army – where compassionate use is already underway. And, this is just the beginning. Listen in as Humacyte’s CEO Dr. Laura E. Niklason tells the Humacyte story.

Tune into this 17-minute chat with Erez Raphael, CEO of DarioHealth (NASDAQ: DRIO).

CDK and RAS-targeting drugs already exist, but in the setting of oncology, if it’s not curative, it’s not enough. As a former practicing oncologist, Onconova’s CEO Dr. Steven Fruchtman knows this and has spent his career at the bench, and now the boardroom, working to improve and provide such drugs for cancer patients. His CDK 4/6 drug, Narazaciclib, a drug with a much-improved toxicity profile relative to competitors, will commence a Phase 1/2a trial in endometrial cancer in Q1 2023. Onconova’s RAS inhibitor, Rigosertib, has shown activity in all flavors of KRAS mutations and is currently being tested in a Phase 2 investigation of checkpoint-resistant NSCLC patients. Tune in for a discussion of the next critical readouts.

Tune into this 9-minute chat with Dror Bashan, President & CEO of Protalix Biotherapeutics, Inc. (NYSE: PLX).

Tune into this 17-minute chat with Martin Welschof, CEO of BioInvent (STO: BINV).

Tune into this 11-minute chat with Raphi Levy, CFO of Alpha Tau Medical Ltd. (NASDAQ: DRTS).

In this 13-minute chat, Amir London, CEO of Kamada Ltd. (NASDAQ: KMDA), discusses the growing commercial business of the company, including six FDA-approved products for rare and serious conditions, and its innovative development pipeline, targeting areas of significant unmet medical need.

In this 15-minute chat, Rob Etherington, President & CEO of Clene, Inc. (NASDAQ: CLNN) discusses the potential for nanosuspensions to improve cellular energy production and treat neurodegenerative diseases, along with Clene’s future directions.

Repairing damage to living tissue often requires the removal or debridement of what was destroyed. This is usually done through surgery—an invasive process performed in a clinical setting that is inherently stressful for the patient. EscharEx is none of that. A topically administered biologic, EscharEx is administered in the outpatient setting, and has been shown to be safe, tolerable, and effective. Listen in as MediWound’s incoming CMO Dr. Robert Snyder describes this innovation.

CTLA-4 was a breakthrough; PD-1—a blockbuster, then IDO got busted and biotech retreated to the bench. It got quiet for a while, but the basic science bounced back, and now we have LAG-3, and on the horizon, a new VISTA. Myeloid cells have the target, and Sensei Bio has the drug. Tune in as CEO John Celebi tells us the story of SNS-101 and why the Fc component is so important.

Endogenous metabolic modulators (EMMs) are composed of amino acids and, when given in combination, have the potential to treat serious disease. With their lead EMM compound AXA1125, a proprietary blend of amino acids, Axcella is posed to address the urgent and growing unmet needs in the settings of long COVID and nonalcoholic steatohepatitis (NASH). For long COVID, Axcella aims to generate ATP for patients sapped of energy, and for NASH, it aims to impact metabolic pathways involved in fat storage. Tune in as CEO Bill Hinshaw explains the mechanisms, promise, and related IP.

Drug discovery is an adventure, drug delivery is an art. The chemists at Lipocine put their experience to the test — by turning drugs with problematic administration into oral agents with improved bioavailability. With validation from their recently approved testosterone replacement drug, Tlando®, and the licensing potential of three other oral assets for NASH and pre-term birth, Lipocine is now focused on developing oral formulations for depression and epilepsy. Tune in as CEO Mahesh Patel, PhD, describes his development plans.

As the American obesity issue grows, the NASH and SHTG treatment markets concurrently expand. At 89bio, the idea is to use nature itself to therapeutically treat this growing problem. Using their lead asset pegozafermin, an analog of the endogenous hormone fibroblast growth factor 21 (FGF21), to restore metabolic homeostasis and thereby reduce liver fat, as well as triglyceride levels, 89bio is currently advancing their development program in both diseases. Tune in as CEO Rohan Palekar gives updates from the ENLIVEN study for NASH and ENTRIGUE study for SHTG, along with future directions in clinical development.

James Oliviero, CEO of Checkpoint Therapeutics, is certain that fortunes can be won by building better and cheaper mousetraps. That’s why he is positioned to capture significant market share with assets for the de-risked oncology targets of PD-L1, with Cosibelimab, and EGFR with Olafertinib.  For Cosibelimab, an anti-PD-L1 antibody, Checkpoint offers an improved mechanism of action and a lower price point. For Olafertinib, a 3rd generation EGFR inhibitor, the play is a better tolerability profile that will boost patient compliance. Building better traps—that’s the bottom line.

The CEO of BrainsWay Ltd, Christopher von Jako, is committed to non-invasive medical technologies – particularly when it comes to the brain. A businessman with over 30 years of experience in medical devices and a PhD in neurology, Dr. von Jako now spearheads the continued development, sales, and marketing of BrainsWay’s Deep Transcranial Magnetic Stimulation (Deep TMS™) device, a non-invasive, highly effective, and broadly reimbursed therapy for major depressive disorder, anxious depression, OCD, and smoking addiction. Tune into Episode 58 of the Benchtop Bios Podcast Series, where Dr. von Jako highlights the device, supporting data, and company’s plans for an international rollout.

It’s the circle of life: the cell cycle is a molecular merry-go-round for the propagation of all cells, including tumor cells. This process is regulated by cyclin-dependent kinases (CDKs), thus, CDK inhibition has long been a goal of drug developers. However, until very recently, toxicity has remained an issue. Early clinical results suggest that Cyclacel Pharmaceuticals has potentially overcome this hurdle. Tune in as Spiro Rombotis, CEO of Cyclacel Pharmaceuticals, describes Cyclacel’s Phase 1/2 studies with its two clinical stage molecules, including lead asset fadraciclib, a CDK2/9 inhibitor, in patients with solid tumor cancers and hematological malignancies.

Artios has raised eyebrows, and cash, raising $320 million since its founding in 2016. Led by CEO, Niall Martin, who spearheaded the development of the PARP inhibitor, Lynparza™, along with the scientific guidance of DDR pioneer, Dr. Graeme Smith, Artios has been able to make a scientific impact. However, in this episode, we will explore their financial impact, as CFO Abid Ansari details how Artios has been able survive and thrive in this challenging market environment.

Most oncology drugs turn things off—Alligator Bioscience prefers to turn things on, specifically, the immune system, by way of stimulation with CD40 and 4-1BB agonists. In this podcast, Alligator CEO, Søren Bregenholt, discusses the latest clinical data for lead anti-CD40 asset, mitazalimab, as well as two distinct 4-1BB agonists in development. Additionally, he answers the critical question: How did you tame the toxicity of these signaling molecules when so many others have failed?

Lowering your LDL levels—so-called “bad cholesterol”—can save your life: an irrefutable observation made possible by the advent of statins. The good news is that we have statins by the bucket-full; however, the bad news is that not everyone can tolerate statins (>20%) or they can’t hit LDL-lowering targets with a statin alone. Enter Nexletol (bempedoic acid) and Nexlizet (bempedoic acid plus ezetimibe) for use alone or in combination with a statin. What’s the global market opportunity for these newly approved agents? (Hint: it’s huge). Esperion’s CEO, Sheldon Koenig tells you exactly how Esperion's discoveries will improve on lipid-lowering treatments, as well as bridge a market gap.

My mother, a woman who thrived on organization, always had her entire medical history in hand when she saw a new healthcare provider—both in hard copy and on disk. No one ever looked at it. Not once. They were not the records of that particular provider and therefore, did not count. And having past test results transferred to a new provider? Good luck with that. Easier to repeat the tests. Not so with patients in the P3 Health Partner systems. Listen in as P3 CEO, Dr. Sherif Abdou, describes his passion, and his plans for refocusing the needs of healthcare where it belongs—on the patient.

Ryvu’s lead asset, discovered-inhouse is RVU120, a CDK8/19 inhibitor with activity in both hematologic and solid tumor cancers currently undergoing multicenter, international testing for AML and TNBC, respectively. With data reported as recently as EHA 2022, pivotal phase II testing will commence in early 2023. As for the platform, with a dual focus on immune-oncology and synthetic lethality—Galapagos wants to take it for a spin, as does Merck, and Ryvu just inked a deal with Exelixis. Give a listen to Ryvu CEO Pawel Przewiezlikowski for all the details…

Using cytokines therapeutically is like firing a shotgun at range – for sure you will hit your target, but off-target effects are likely, if not certain. To hit your target exclusively you have to get close. Delivering a proprietary version of the chronic inflammatory cytokine IL-10 encoded on a proprietary plasmid, injected locally, gets you really close. Using their non-viral, non-integrating vector, Xalud Therapeutics is exploring the use of IL-10 for osteoarthritis (FDA fast tracked), and other chronic inflammatory conditions, including ALS, MS, and neuropathic pain, with data from over 300 OA patients already in hand.

An inch wide and a mile deep—that’s the sort of expertise CSO of Artios Pharma, Dr. Graeme Smith, brings his benchtop. Since his time at Cambridge, Smith has been laser focused on DDR mechanisms, first elucidating, and then translating those observations to create the PARP inhibitor drug, Lynparza. Developed at Kudos Pharma, and later, AstraZeneca, hear Smith recall his “aha” moment for this first-in-class blockbuster drug, as well as his descriptions of his two new DDR-targeting, clinical stage assets developed at Artios that leverage his knowledge of novel DDR pathways—including those that will overcome resistance to PARP inhibition.

Hypoxia is the key. TEC-001 is a prodrug selectively activated in hypoxic environments, such as that induced by the long-known technique called trans-arterial embolization, a procedure that shuts off blood supply to tumors and thereby creates a low-oxygen, hypoxic environment. Delivered directly to the tumor bed through a tumor-feeding artery, hypoxia-activated TEC-001 then converts into free radicals that cause so-called immunogenic cell death (necrosis, as opposed to apoptosis) which enables immune cells—boosted with immunotherapy—to seek out and destroy tumor cells both locally, and throughout the body. CEO Ray Lee, M.D., Ph.D., explains.

A car is a very efficient delivery system until you can’t find a place to park, or the spot you find is nowhere near where you wanted to go. For medicine, getting to the right place, and getting there in time is critical. With the iSPERSE platform you can reformulate known drug entities—compounds that have already been de-risked—for fast-acting pulmonary distribution using most any inhaler device. Listen to the POC work already in hand for migraine, and COPD as described by Pulmatrix CEO Ted Raad.

MDM2 is a key regulator of p53, the protein responsible for tumor suppression and apoptosis — an intractable, yet undruggable target. Previous attempts to drug MDM2 have been met with significant toxicities issues. The MDM2 oral inhibitor milademetan has the potential to address these issues and in doing so may open the door to treating multiple tumor types, as identified by standard molecular testing. Indeed, studies with milademetan have demonstrated promising preliminary results in liposarcoma. Let the Wall Street veteran, CEO Avanish Vellanki, walk you through the RAIN.

The only people that like infusion suites are those who own them. Payers don’t like them. Patients hate them. But for many drugs, due to their molecular nature there is simply no choice, and this has been the case with the class of drugs known as checkpoint inhibitors—until now. Now there is Envafolimab, a novel anti-PD-L1 antibody from Tracon Pharma with a low volume, subcutaneous administration that is already being tested in the clinic in multiple indications. Listen in as CEO Charles Theuer describes his licensing strategy that brought Envafolimab, as well assets targeting CTLA-4, CD73, and DNA repair mechanisms on board.

By way of an exquisite toggling of activity, HADUVIO stimulates one opioid receptor (kappa) and blocks the activity of another (mu) while avoiding the engagement of the third (delta). The  objective of this combination of receptor activity is to decrease chronic cough due to Idiopathic Pulmonary Fibrosis, or severe itch due to Prurigo Nodularis. Phase II data are available for both development programs,  which CEO Jennifer Good has proudly shared—along with a story of how Trevi got its name…

If the pandemic taught us nothings else, we’ve learned the critical importance of having a dependable system for delivery. OncoNano offers two such systems (read: platforms). The first, ON-BOARD, is a polymeric micelle that delivers its therapeutic payload only in the acidic environment of a tumor bed. The second, OMNI, consists of a polymer that in itself stimulates the immune-activating STING pathway, and which can further be loaded with other STING agonists, or, potentially, other mechanistically relevant oncology agents. POC phase II trials are underway…

Along with the first-ever approval by the FDA of a so-called checkpoint inhibitor, the anti-CTLA-4 drug Yervoy, in 2001, came vindication; the treatment modality of immuno-oncology (IO) had arrived. Anti-PD-1 drugs soon followed with even greater—far greater impact. But then came some failures, and the presumed bright future of other IO assets began to dim. Until now. The first LAG-3-targeting drug was recently approved, and as of ASCO 2022, Immutep’s LAG-3 asset is poised to replace IO/chemo in the front-line setting for NSCLC. Hear CEO Marc Voigt parse the data, and describe the development program going forward.

There’s no point in receiving a gift you can’t keep, be it a pony, or a therapeutic. For the latter to be effective it must be retained, yet the immune system can’t discriminate between friend or foe; there is only you, and not you, and not you is simply not tolerated. Enter ImmTOR®, a nanoparticle technology that aims to tolerize the immune system to the target of choice – a gene therapy, a biologic, or in cases of autoimmunity – you. With buy-ins from the likes of Takeda, Sarepta, Sobi and AskBio, it’s worth it to find out more about Selecta Biosciences.

There’s nothing new about transdermal delivery of drugs—patches, gadgets, and solvents abound—but each has physical limitations, and the drugs themselves may not be amenable to a particular approach. Enter a novel drug formulation platform by Dyve Biosciences. Delivered in what appears to be a cosmetic cream, Dyve has two POC clinical trials underway: Gout, to test local delivery of a drug; and cancer, testing the same drug that can only be delivered through the skin, and targeting the tumor microenvironment (with a buy-in from Moffitt Cancer Center). CEO Dr. Ryan Beal explains…

In pharmacology, getting your drug to where it’s needed is everything. In immunology, to elicit an immune response that location is often the lymph node, and the point of delivery are antigen presenting cells. Amphiphile, from Elicio, can make that happen. Whether the cargo is DNA, a peptide, or a small molecule, once linked to the Amphiphile moiety, the construct is taken up by the lymphatic system. First asset in the clinic? A multiple antigen therapeutic for mKRAS.

Innovation can sometimes be counterintuitive, as in the case with Tyrvaya, a drug approved in 2021 for the signs and symptoms of dry eye disease that is a nasal spray. And how does that make sense? Well, it makes sense because Tyrvaya ®, a cholinergic agonist to treat the underlying, and sometimes debilitating disease. Hear Dr. Jeffrey Nau, ophthalmology expert and CEO of Oyster Point explain…

The allure of allogeneic “off-the-shelf” adaptive cell therapy (ACT) is obvious – by definition, the treatment is immediately available, and due to the nature of batch manufacture versus the one-off creations of an autologous ACT, it will very likely be cheaper. The question remaining is what cell type is best to use for clinical efficacy – T cells of the adaptive immune system, or natural killer (NK) cells of the innate system, OR, just maybe, a cell that does both – the CAR NKT cell therapy, from Athenex. Hear Dr. Daniel Lang, President of Athenex Cell Therapy, explain how this is possible.

Having focused on endocrine disorders since grad school, first at the bench and later in the board room, Dr. Thierry Abribat founded and became the CEO of EU-based Amolyt Pharma because he wanted to have a “social impact” – he wanted to make a difference. With two clinical stage, biologic assets in hand (and an orphan drug designation) Abribat is hoping to address the serious unmet needs of patients with hypoparathyroidism and acromegaly.

Everyone is excited about KRAS, the “undruggable” target that now has a drug. However, that drug only hits one specific, rather rare KRAS mutation, leaving the vast majority of patients with KRAS mutant variants who, after exhausting standard of care (SOC), are left without any effective treatment options. So, what if you had a drug that hit just downstream in the KRAS pathway, and further, was synergistic with SOC – wouldn’t that serve all such patients? Yes. Yes, it would. That drug is called Onvansertib, from Cardiff Oncology.

Hear how Jay Mei, MD, PhD, went from his benchtop years at the NIH to a blockbuster launch at Celgene (think, Revlimid, after stints at Novartis and J&J along the way) – to spearhead the multi-asset juggernaut that is the oncology company, Antengene. From it’s “license and build” beginnings, to the advent of in-house programs (15 assets in all) Antengene is poised to hit multiple oncology targets, from a small molecule ERK 1/2 inhibitor, to a bispecific for PD-L1/ 4-1BB. And did I mention they have a global license, and are expanding indications for XPOVIO? Give a listen…

Proteins designed as drugs – the so-called biologics – sparked a medical revolution, but it has come at an extraordinary cost: less than 2% of Americans use these drugs, yet they account for 40% of total spend on prescription medications. Something’s got to give. Mark Emalfarb of Dyadic thinks that something is manufacturing, and his something is C1 – a protein manufacturing platform, and cell line that can produce biologics cheaper and faster than anything out there. Unconvinced? Give a listen.

Having the ability to activate a precise, robust and persistent immune response to kill cancer cells is what IMV is all about. Using its DPX delivery technology, IMV’s immunotherapies are easy and cost-effective to manufacture. With promising clinical data now available, their lead compound is well tolerated and effective in several cancer indications including solid cancers (ovarian and bladder cancers) and DLBCL (lymphoma). What else is cooking at IMV? Former professional chef, and IMV CEO, Andrew Halls gives us a taste…

There are approximately 30 million individuals in the U.S. currently living with one of at least 7,000 rare diseases. The National Organization for Rare Disorders estimates that more than 90% of these patients are still without an FDA-approved treatment. Dr. Jane Larkindale, VP of Clinical Science at PepGen, Inc. is looking to change that, and she has both the experience and passion to show you how.

A scar is proof you survived – a good thing. Uncontrolled scarring, called fibrosis, is a threat unto itself (think cirrhosis) or an impediment to clinical intervention (think macrophages, T-cells and cancer). Mechanisms that drive both involve the molecule, Gal-3, and an enzyme, LOXL2. The mission of Galecto is drugging these targets with small molecule, first-in-class inhibitors. Hear how Galecto’s CEO, Dr. Hans Schambye, made their mission his own.

In oncology, the field of neoantigen prediction is rife with proprietary mathematics for homing in on the best antigens for T cell activation. Only one neoantigen platform, ATLAS, from Genocea, tells you not only about what activates, but also what antigens/epitopes suppress that T cell activity – so called, “inhibigens”. With his platform recently validated in Cancer Discovery, Chip Clark, CEO of Genocea, explains the investment opportunity that is ATLAS.

Every cancer neoantigen prediction platform has lots and lots of math – the PIONEER platform, from the Danish company, Evaxion, has data. In a phase I/IIa study in metastatic melanoma the ORR was 67%, and two patients with stable disease converted to complete responders. Investors take note, because Merck sure did… Dr. Lars Wegner, CEO of Evaxion fills in the details.

Not enough fluids? Drink more. Too much fluid – entirely different, far more complex problem. From the systemic swelling caused by congestive heart failure to the localized ascites caused by cancer, or NASH, Sequana Medical has developed novel approaches to drain the fluid away when diuretics are no longer effective. The results are greatly improved clinical outcomes and quality of life for patients, and significant cost savings. Ian Crosbie, CEO of Sequana Medical, Oxford graduate, and long-time financial-world veteran, explains it all.

Turning a biological process on or off is like flipping a light switch. However, these approaches often come with serious side effects that can limit therapeutic utility. For this reason, treating certain types of CNS disorders like chronic pain, PTSD, and cognitive impairment requires a more nuanced modulatory approach to restore normal brain function. Listen in as Aptinyx’s newly minted president & CEO Andy Kidd, MD explains how the company is taking a novel approach to NMDA receptor modulation to help create a platform of small molecules aimed at restoring normal brain balance to address a host of serious neurological disorders.

Harpreet co-founded Immatics in 2000 to translate pioneering scientific discoveries in immunology into highly innovative immunotherapies to impact the lives of cancer patients.

Hear how Captor Therapeutics became a Swiss/Polish public biotech company run by a Scotsman –as told by 30-year healthcare industry veteran and Captor’s CEO, Dr. Tom Shepherd. That’s one great story – another is how Captor’s targeted protein degradation platform will stick it to the competition with their ligase library, and proprietary molecular glues and bifunctional degraders...