Kevin Marks

The ZEPHYRUS-1 trial led by testing pamrevlumab (CTGF antibody) for #PulmonaryFibrosis published negative results yesterday, also discontinuing ZEPHYRUS-2. JAMA has a good editorial on challenges and ideas for improving predictive validity for #IPF clinical trials: - One is that the IPF label covers a heterogeneous patient population. Genetic risk factors could be used for targeting drugs, though that leaves >70% of patients with no treatment. Broader -omic characterization of patients & preclinical models could reveal which models best match patient subgroups. - Another is the FVC endpoint. Many physicians argue for more nuanced endpoints. But while we're using FVC we should think about how preclin assay map to this, given that it can't be measured in typical rodent models. Larger animals could give more direct comparisons, or when that's not feasible then we should think carefully about how anatomy and pathobiology of models reflect this endpoint. - Preclinical models for are much maligned, with high false positive rates for standard bleo mouse model. The editorial authors suggest focusing on human organoids, although this may be throwing out the baby with the bathwater: IPF is an inflammatory disease with a key role for immune cells, which aren't included in organoid/chip models (yet anyway)... We should also think about in vivo models that address the obvious limitations of the standard bleo mouse model: 1) fibrosis resolves spontaneously, instead of progressing. 2) IPF is strongly age-related, but the mice are usually young. Other species (even rats) have less spontaneous regression of fibrosis, and multiple types of injury might better capture patient exacerbations. And using older animals could capture both known and unknown mechanisms preventing normal regeneration in PF patients. Gordian Biotechnology's Vishwaraj Sontake thinks a lot about predictive validity for complex diseases like IPF. Mapping models to patients is key, and the basis for our 'Patient Avatars' concept. Trials are were biopharma spends the most dollars, so we think it's worth spending more on doing R&D in predictive models. Editorial: https://lnkd.in/gRUFQ5XK

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In September, the results of the Phase III trial of biospecific antibody Ivenescimab delivering a meaningful improvement over Merck’s Keytruda in lung cancer sent Summit Therapeutics (NASDAQ: SMMT) stock soaring. However, few paid attention to the originator of the PD-1/VEGF targeting asset, Chinese biotech Akeso Bio. Akeso represents a cohort of emerging innovative drug companies from China, working at impressive speed to deliver advancements in patient care and next-generation therapeutics with global ambition. #deeptech #chinesedeeptech #bosonventures #Ivenescimab #biotech #immuology

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𝗪𝗵𝗲𝗿𝗲 𝘄𝗶𝗹𝗹 𝗯𝗶𝗼𝘁𝗲𝗰𝗵 𝗶𝗻𝘃𝗲𝘀𝘁𝗺𝗲𝗻𝘁 𝗺𝗼𝗻𝗲𝘆 𝗴𝗼 𝗻𝗲𝘅𝘁 𝘆𝗲𝗮𝗿? According to Pitchbook...... * 𝗣𝗵𝗮𝘀𝗲 𝟮 and later clinical stage companies. Risk aversion is diminished the later the stage, and deeper pockets now prefer conservative bets. * 𝗚𝗟𝗣-𝟭 related obesity drugs. Now an obvious target pathway, many are trying to enter ASAP. Competition is for a $70 Bn market, but who can beat the global manufacturing capacity of Lilly or Novo? * 𝗚𝗲𝗻𝗲𝗿𝗮𝘁𝗶𝘃𝗲 𝗔𝗜. Still buzzy over the past 3 years, even though utility that leads to enhanced clinical success is still not so obvious yet. Application to predictively create potent Biologics is a major theme. I suppose any.asset that is a mid/late stage, GLP-1 obesity biologic, created by generative AI, will be the preferred word-salad for box-checking investors in the year to come. If Pitchbook 2025 prophecy is correct, then for everyone else currently seeking reduced early stage investments - "𝗦𝘂𝗿𝘃𝗶𝘃𝗲 𝟮𝟬𝟮𝟱" might be the motto for next year. Let's hope it does not turn out this way. 𝗙𝗶𝗲𝗿𝗰𝗲 𝗕𝗶𝗼𝘁𝗲𝗰𝗵 𝗿𝗲𝗽𝗼𝗿𝘁𝘀- " Against an economic backdrop of rising interest rates and tighter capital markets, PitchBook doesn’t expect investors’ appetite for companies with “clearer paths to monetization or Big Pharma acquisition” to wane any time soon. "

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How do we minimize the number of protocol amendments and increase the operational feasibility of our clinical trials? This article below points out the benefits of using data, conversations and real world data to enhance the feasibility of the protocol design and inclusion/exclusion criteria: 1) Are we being too strict on our criteria in order to "control" for data variability? 2) Do are criteria allow for the intended patient population in the real world (if not, they need to) 3) How realistic is your design in how the study sites actually work? How they see and treat patients? How is your company ensuring the design meets these requirements? https://lnkd.in/gzJzFd-3

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Fast-forward 10 years when every bio company has access to highly performant models for in silico molecular design... Assuming this translates into many more high quality candidate molecules, there will be insatiable demand for already-scarce clinical development talent. Clinical development skillsets will become multiples more valuable. An optimist might argue we need to start preparing our clinical development regulatory and operational infrastructure for materially higher throughput.

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I've been spending a lot of time thinking about the productivity problem in life sciences R&D - which, in my opinion, seems to be the single biggest problem to solve in all of life sciences.   Inefficiency takes on an entirely new meaning in biopharma vs. other industries where it simply amounts to sunk cost. In biopharma - particularly for the long tail of smaller biopharmas - it can be the difference between missing and meeting milestones, securing and not securing funding, life and death. Being efficient is increasingly a requirement for survival. Tech certainly isn't a golden bullet, but we see a lot of opportunity for it to help move the needle, especially if it's in combination with behavioral/cultural change.   Over the last month or so I've been sharing our high-level thoughts on this topic through a series of blog posts, the last of which was published today (see comments for links to the prior two posts). This really only begins to scratch the surface on our thinking here and we're eager to chat with folks in greater detail. If you’re working in this space or have insights to share, I'd love to hear from you! https://lnkd.in/g9EsD5b3

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Alentis therapeutics’s anti-Claudin 1 antibodies in oncology and fibrosis have the potential to not only tackle a broader range of tumours than Claudin18.2 and Claudin6 but also to tackle the extracellular matrix remodelling that occurs in certain cancers which helps to exclude T cells in the tumour microenvironment. The data nicely summarised below from ESMO highlighted the potential of the tight junction Claudin family of proteins in oncology. Alentis is also now in the clinic aiming to showcase the potential for blocking the actions of Claudin1 in fibrosis. It is an exciting time for this next tight junction protein, Claudin1, as it moves into the clinical limelight. Alentis leads the way as a first in class.

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🚨 The #FDA's latest draft guidance on accelerated approvals takes aim at "dangling" approvals—products still marketed despite failed confirmatory trials. The agency is now mandating tighter timelines (2-4 years for oncology), more transparency in withdrawal processes, and public involvement. 🕵️‍♂️ This marks a shift from flexibility to rigor, signaling that the accelerated pathway is no longer a free pass. For #biopharma, it's both a challenge and an opportunity to align trial strategies earlier. Is this the FDA tightening the reins—or just evolution in regulatory science? FDA website: https://lnkd.in/gqc-z-5e #pharmanews #breakingnews

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There is a lot of advancement happening globally using the tools of AI. In drug discovery, using AI in an appropriate way to build a pipeline of effective solutions for patient health - therapeutics and diagnostics - that is where the rubber meets the road. Pipeline is key.

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Excellent way to spend 1 minute, 30 seconds. DSO shares via an embedded video in the article below how Modality.AI is making an impact with patients. It is wonderful to have NIH SEED as a partner on this journey. Relentless Venture Fund David "DSO" Suendermann-Oeft #Neurotech #AI #BIO2024 #precisionmedicine #clinicaltrials #healthtech #healthcare #digitalhealth

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When investors think your gene therapy isn't good enough... That's what Lexeo is feeling right now on LX2006 for cardiomyopathy associated with Friedreich's Ataxia. Their Ph1/2 trial saw 50% of patients (8 total in the trial) experience a reduction of 10% in left ventricular mass index. There are only a handful of companies developing therapies for Friedreich's Ataxia, let alone the heart-related components of this rare disease. While Lexeo was optimistic about the data and taking it to discuss a future pivotal study with regulators, the market was not, knocking the stock down at present ~25%. The public markets are brutal with earlier stage companies. Depending on capital needs, it can be a bit easier to not be public when you're early in development. Regardless, another piece of positive news for AAV as it slowly comes out of its winter. Lines up with our beginning of the year predictions below! https://lnkd.in/drRreSCd

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Pharma/Biotech Roundup 🔃 Septerna: Upsized IPO raises $288M to support pipeline of GPCR Drugs Alpha-9 Oncology: Announces $175 Million oversubscribed Series C Financing to advance clinical pipeline of radiopharmaceuticals AvenCell: Raises $112 Million in Series B; Funding led by Novo Holdings Lyell Immunopharma: To acquire ImmPACT Bio and prioritize their pipeline in order to concentrate on next-generation CAR T-cell therapies. Set to discontinue the development of LYL797, LYL845 and earlier-stage TIL programs GSK: Investing up to $800 million to double the size and capacity of its production site in Marietta, Pennsylvania Sanofi: Continuing to move forward to sell a 50% stake in Opella to CD&R Monopar Therapeutics Inc.: Finalizes an agreement with Alexion Pharmaceuticals, Inc. for an exclusive license to ALXN-1840, a drug candidate for Wilson disease Alto Neuroscience: Stock has dropped by over 60% after Phase 2b trial of their lead drug candidate in depression failed to meet primary goals Merck: Acquires Modifi Bio and brain cancer assets for $30M

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Thank you to Endpoints News for great coverage today of Breakout Ventures portfolio company Immusoft's positive results for the first patient ever dosed with an engineered B cell therapy. The company held a webinar yesterday with KOLs (Paul Orchard, Paul Harmatz), patient advocates (Mark Dant) and our partners at CIRM (Abla Creasey). HIGHLIGHTS:  This was an MPS I adult patient, treated at the lowest dose. While a pediatric disease, this is the standard protocol. But means that expectations were low and safety was goal. The patient remained on standard of care Aldurazyme (ERT) but then took a holiday at 8 months. The treatment required 𝙉𝙊 𝙥𝙧𝙚𝙘𝙤𝙣𝙙𝙞𝙩𝙞𝙤𝙣𝙞𝙣𝙜/ 𝙞𝙢𝙢𝙪𝙣𝙤𝙨𝙪𝙥𝙥𝙧𝙚𝙨𝙨𝙞𝙤𝙣. So even at dosing, we knew this patient would experience none of the adverse events associated with the toxicity of other treatments and did not have to spend the associated time in the hospital. Since the patient was dosed November 2023:  - 𝙏𝙝𝙚𝙧𝙚 𝙝𝙖𝙫𝙚 𝙗𝙚𝙚𝙣 𝙣𝙤 𝙖𝙙𝙫𝙚𝙧𝙨𝙚 𝙚𝙫𝙚𝙣𝙩𝙨  - confirming the safety profile - 𝙐𝙧𝙞𝙣𝙚 𝙂𝘼𝙂𝙨 𝙛𝙚𝙡𝙡 𝙞𝙣𝙩𝙤 𝙩𝙝𝙚 𝙣𝙤𝙧𝙢𝙖𝙡/𝙝𝙚𝙖𝙡𝙩𝙝𝙮 𝙧𝙖𝙣𝙜𝙚 𝙗𝙚𝙩𝙬𝙚𝙚𝙣 3-8 𝙢𝙤𝙣𝙩𝙝𝙨 after treatment. For context, in Aldurazyme’s clinical trial, none of the patients reached normal urinary GAG levels.  - 𝙃𝙚𝙥𝙖𝙧𝙞𝙣 𝙨𝙪𝙡𝙛𝙖𝙩𝙚 𝙞𝙣 𝙩𝙝𝙚 𝘾𝙎𝙁 𝙬𝙖𝙨 𝙙𝙤𝙬𝙣 25% 𝙖𝙩 6 𝙢𝙤𝙣𝙩𝙝𝙨, noting that the FDA has used this as an acceptable surrogate endpoint in MPS.  - 𝙏𝙝𝙚𝙧𝙚 𝙬𝙚𝙧𝙚 𝙨𝙪𝙧𝙥𝙧𝙞𝙨𝙞𝙣𝙜 𝙛𝙪𝙣𝙘𝙩𝙞𝙤𝙣𝙖𝙡 𝙞𝙢𝙥𝙧𝙤𝙫𝙚𝙢𝙚𝙣𝙩𝙨. These are adult patients, who are often struggling with the stiffness and lack of mobility that happens as the disease progresses. The patient saw a 30% 𝙞𝙢𝙥𝙧𝙤𝙫𝙚𝙢𝙚𝙣𝙩 𝙞𝙣 𝙖 6 𝙢𝙞𝙣𝙪𝙩𝙚 𝙬𝙖𝙡𝙠 𝙩𝙚𝙨𝙩 𝙖𝙣𝙙 𝙖𝙣 𝙞𝙣𝙘𝙧𝙚𝙖𝙨𝙚𝙙 𝙧𝙖𝙣𝙜𝙚 𝙤𝙛 𝙨𝙝𝙤𝙪𝙡𝙙𝙚𝙧 𝙢𝙤𝙩𝙞𝙤𝙣 𝙖𝙩 6 𝙢𝙤𝙣𝙩𝙝𝙨. Truly rewarding to see this sort of outcome in a patient. We are thrilled for what this could mean for all MPS I patients and the potential of b cells as therapy. Excited for this next phase for Immusoft and always happy to connect those of you who have been following the story directly to the company. 

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By leveraging AI with vast genetic databases, we are not only quickening the pace of identifying potential drug targets but also enhancing the accuracy of clinical diagnostics and predictive modeling. Recently, I had the privilege of discussing the profound impact AI is having on pharmaceutical R&D with Kim Branson, GSK's SVP Global Head of Artificial Intelligence and Machine Learning. Listen on Raising Health: https://lnkd.in/g6QUm2-A

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There's a deep personal history for me with this major acquisition today. Incyte (Rich Levy) had the vision at the time (2016) to let me design a very bold #phase2 #clinicaltrial with topical #ruxolitinib which ended up being the first FDA-approved JAK inhibitor in dermatology as OPZELURA® (ruxolitinib) HCP. Incyte acquires John E. Harris, MD, PhD's Villaris Therapeutics backed by Medicxi to go after #vitiligo. John E. Harris, MD, PhD and I are co-founders of Alys Pharmaceuticals which is going after #urticaria #itch #vitiligo and beyond again backed by Medicxi. In parallel in 2019, we publish an early and key paper in the journal Immunity (Meixiong et al. Immunity 2019) with Xinzhong Dong who discovered MRGPRX2 (actually, the entire family). I then start advising Escient Pharmaceuticals with the most bullish optimism about MRGPRX2 as target for #skin #diseases and witness a brilliant execution by Veena Viswanath et al. Incyte makes a bargain acquisition today for $750 million to transform skin disease in #dermatology and #allergy. The key point here is that MRGPRX2 antagonist will NOT be competing IMO with other more moderate-to-severe assets in #CSU like #barzolvolimab. They will mutually grow the market for #CSU across the mild to severe spectrum in a disease that is growing in incidence and poorly penetrated even by great drugs like #omalizumab. Keep in mind, #antihistamines are >$2 billion annual sales for #itch, which it does not even work for that well! This will accelerate new treatments for #urticaria and much beyond. Great for our patients.

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Anavex Life Sciences (NASDAQ: AVXL) reports an impressive effect size for their Sigma-1 receptor agonist (activating autophagy), slowing Alzheimer's progression in a Ph2/3 study. https://lnkd.in/efc5r4kr https://lnkd.in/eWvWcQXG "Anavex Life Sciences (NASDAQ:AVXL) added ~13% in the premarket on Thursday after the neurology-focused drug developer said its lead asset blarcamesine (ANAVEX 2-73) slowed Alzheimer's disease progression by more than a third in a Phase 2/3 trial. Based on 48-week data from the trial, the New York-based biotech said blarcamesine, a once-daily oral therapy targeted at an Alzheimer's-linked protein called SIGMAR1, slowed clinical progression by 36.3% in terms of the primary endpoint. The effect was even more pronounced in a subgroup of patients identified as SIGMAR1 wild-type group, with blarcamesine slowing Alzheimer's progression by 49.8% at 48 weeks compared to the placebo group. The company remains on track to file regulatory submissions for the drug in Europe this year. Anavex (NASDAQ:AVXL) presented the data readout at a medical conference focused on Alzheimer's Disease in Madrid, Spain." Compared to Lecanimab, an FDA-approved anti-amyloid antibody (27% decline reduction on ADAS-Cog over 18 months vs. 38% (50 mg group), 26% (30 mg group), and 49% (Sigma 1 receptor WT subgroup). Lecanimab has significant side effects and is expensive compared to Anavex's small molecule.

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Risk v. Return Investment Profile: ImmunoPrecise Antibodies Ltd.(NASDAQ: IPA $0.625) CFP has had the opportunity to review Carl Kestens' Fair Value Analysis of ImmunoPrecise(attached below). CFP would encourage all of you to review it as well. CFP's key takeaways and comments are: 1. ImmunoPrecise has a Market Cap of approximately $18 million USD, which is extremely cheap relative to any market evaluation technique you use. 2. IPA has several potential growth drivers that have yet to deliver value to the company. 3. We agree that many investors have given up(lost patience) on the prospects of any of these potential events will actually be achieved. Expectations of Investors have not been met by the Company to date. Herein may lie the opportunity moving forward... 4. IPA has finally addressed its non-existent Capital Markets Strategy with an experienced, and seasoned group out of New York City over the last couple of weeks. 5. The NYC Group is also addressing the Company's Communication, Media, and Investor Relations Strategy. The new messaging(which should have always been in place) is under promise, and over deliver(exceed expectations) go forward. CFP has already seen improvement in the messaging to "simplify" the story to prospective investors. 6. The investment risk/return profile today looks very compelling. It reminds me of some old investment advice: "buy when everyone is selling and sell when everyone is buying." Disclaimer: This is posted for information purposes only. Please consult your investment professional for investment advice. Capital Find Partners owns shares in ImmunoPrecise. IPA (ImmunoPrecise Antibodies) BioStrand (a subsidiary of IPA) InterSystems Quantum Media Group, LLC #LENSai #Biotech #ai #HYFTs #HYFTTechnology #drugdiscovery #healthcare #pharma #personalizedmedicine #omics #AIDrugDiscovery #systemthinking #bioinformatics #antibodies #machinelearning #multiomics #LLMs #datascience #computationalbiology #nlp #ontologies #semantics #knowledgegraphs #lifesciences #bigdata #informationinformationdilemma #patternrecognition #insilico #molecularbiologists #aminoacids #dna #rna #HYFTpatterns

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MassBio CEO & President Kendalle Burlin O'Connell, Esq. recently spoke with Adil Ali, MD and Onyx about representing the world's most consequential life sciences ecosystem, MassBio's Vision 2030 strategic roadmap, programs like #MassBioDrive and BioversityMA, and more. Onyx's in-depth report, Vital Signs: Future of Healthcare, will appear in Fortune magazine in December ahead of JPM Week. 🔗: https://lnkd.in/eVkggiwv

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