Sean McClain

Wow - 2 ex-Meta employees launch EvolutionaryScale landing $142m to advance AI in biology. EvolutionaryScale has introduced ESM3, a cutting-edge language model for biology that predicts protein sequences, structures, and functions. This model can simulate millions of years of evolution, generating new proteins with potential applications in medicine, research, and sustainability. ESM3 represents a significant advancement in AI's ability to design and engineer biological systems. There will be comparisons with AlphaFold3, intrigued where this goes... https://lnkd.in/dhtQDtsA #AIinDrugDiscovery #genomics #proteomics

3

1 Comment

Artiva Biotherapeutics, a clinical-stage NK cell therapy biotech, is trying again for the public markets, it revealed Friday afternoon in an #SEC filing. The San Diego biotech is going for a Nasdaq debut but in a very different biotech financing environment than when it originally sought an #IPO in the spring of 2021, at a time when large public floats were easier to achieve thanks to low interest rates and generalist investors’ intrigue in drug development. And this time around, it’s without partner Merck, which axed their CAR-NK solid tumor collaboration last October, according to Friday’s S-1 filing. #NKcelltherapy #celltherapy #cellandgenetherapy #advancedtherapies #publicmarkets #biotech #biotechnology #financing #funding #lifescience #lifesciences #IPOs #solidtumors #bloodcancers #autoimmunedisease GC Cell 5AM Ventures venBio RA Capital Management

41

1 Comment

I came across a stunning Illumina research report yesterday. It was written by well respected, long-time Illumina analyst Jack Meehan, CFA way back in November 2020 - two months after Illumina announced its intention to acquire GRAIL - and 9 months before it closed the deal. The 50 page detailed report is amazing because Jack and team basically foresaw all the downside risks of GRAIL that have since come to fruition. They were so confident the deal was bad that they advised their clients to SELL their Illumina stock (which was then at >$300). The report summary is very clear: "We do not agree with the strategic merits of Illumina's proposed acquisition of GRAIL. We have now completed our comprehensive review and believe GRAIL’s clinical data has shortcomings. We also think this is as good as it's going to get, and headline data could deteriorate in the future. From our discussions with leading scientists and reimbursement experts, we struggle to see how Galleri will earn broad coverage. WE NOW THINK GRAIL IS VALUE-LESS UNTIL PROVEN OTHERWISE". You can see the arc of their reasoning simply in the table of contents: - The Reality: GRAIL's Clinical Data Has Shortcomings - You Don't Have to Take Our Word For It... Experts Agree - We Think Headlines Could Get Worse with Subsequent Publications - Payors Have Historically Raised Concerns that Screening Tests Increase Risks and Raise Health System Costs - GRAIL is a Cash Burning Machine, and Consensus is Too High - So Why is Illumina Acquiring GRAIL? There are No Good Answers Fascinating to me that THIS WAS ALL FORESEEABLE by smart people working with public information 🤯🤯🤯

206

27 Comments

"The hype will play out in the long term," James Fraser said. "The hard part of drug discovery (is) it's a pretty long business. You can't take the wet lab part out of it yet. Stuff needs to play out in the clinic." Ron Leuty takes an in-depth look at Profluent and how #AI has become a force in drug development (biologics & small molecule). We are seeing this play out in applications to the QB3 mentoring program. It is striking how many new companies are touting that their use of AI/ML provides a competitive advantage. It's almost more remarkable if a drug discovery company is NOT using AI. And it is very hard to judge the longer-term commercial prospects of a new company whose approach relies on AI/ML. Obviously the quality of the data the models are using is paramount. Anyone with thoughts about how to assess these companies, please weigh in! https://lnkd.in/gaVr3CPj

18

My favorite new obsession in the NY Times! These new genAI drug dev companies are going to need lots of training data and that's bullish for everyone in the LS tools chain from biobanks to instruments to bioinformatics 🥳 "The companies are leveraging the new technology — which learns from huge amounts of data to generate answers — to try to remake drug discovery. They are moving the field from a painstaking artisanal craft to more automated precision, a shift fueled by A.I. that learns and gets smarter." "Just as popular chatbots like ChatGPT are trained on text a cross the internet, and image generators like DALL-E learn from vast troves of pictures and videos, A.I. for drug discovery relies on data. And it is very specialized data — molecular information, protein structures and measurements of biochemical interactions. The A.I. learns from patterns in the data to suggest possible useful drug candidates, as if matching chemical keys to the right protein locks." "Generative A.I. can then digitally design a drug molecule. That design is translated, in a high-speed automated lab, to a physical molecule and tested for its interaction with a target protein. The results — positive or negative — are recorded and fed back into the A.I. software to improve its next design, accelerating the overall process." The article is all about Terray Therapeutics (who do they know at the NYT 😳) but mentions Recursion, Schrödinger and Isomorphic Labs. But hey Xaira Therapeutics your founder David Baker is quoted but you don't get a mention🙀I think it's because no one can spell your name but maybe David just needs media torture, I mean training 🤣

50

19 Comments

I’m thrilled to announce the launch of Radar Therapeutics, dedicated to making programmable, safe, "smart" #mRNA-based therapies that only get activated in the right cells, at the right time. Working with Katherine Jones, Sarah Chesemore, and others at the Bill & Melinda Gates Foundation, we witnessed how Moderna and BioNTech SE/Pfizer catapulted mRNA therapies onto the world stage with unprecedented speed, saving millions of lives.   At Radar, we want to bring this promise beyond vaccines into the most complex therapeutic compartments by solving one of the biggest problems for these therapies: making sure these mRNAs only reprogram the right cells in the body, avoiding potentially toxic off-target effects. We are committed to making therapies with the highest bar of safety, and widely accessible to patients that need them. I was incredibly lucky to meet my co-founder Eerik Kaseniit (thank you Anna-Julia Storch), while at Stanford University Graduate School of Business. Eerik was obsessed with the problem of precisely targeted, timely and controlled regulation of mRNA translation. Alongside Stanford Prof Xiaojing Gao and MIT Prof Jim Collins, we decided to direct those efforts towards saving lives by starting Radar Therapeutics. We attracted the brilliant minds Svetlana Lucas, David Schaffer, and Eric Klein along the way. We are grateful to NFX, Eli Lilly and Company, Biovision Ventures, and KdT Ventures for taking the lead on this round, alongside BEVC, Pear VC, ARTIS Ventures, Ten VC, Elementum Ventures, Emcure Pharmaceuticals Limited, SALT, Conscience VC, and more. Here’s to a future where we can program therapies to rewrite any disease with utmost safety and accuracy. I’ll be at #BIO2024 for anyone looking to connect! Sharing some information about the company here: Endpoints News - https://lnkd.in/g4MQT245 Firstword Pharma - https://lnkd.in/gq3heWsE Genetic Engineering News - https://lnkd.in/gNPDfHEs Chemical & Engineering News - https://lnkd.in/gUx8ijmY Longevity Technology - https://lnkd.in/gRwdtiKx PBR- https://lnkd.in/gvUG_c5M Businesswire - https://lnkd.in/gcv88QAM Alix Marduel Vasudev Bailey Asset Abdualiyev Shan-Lyn Ma Wesley Barrow Pioneer Fund Jackie Benson Shannon Dahl Jackie Papkoff, Ph.D. Nat Kolber Jon Levin Ilya Strebulaev StartX Ron Boger Howard Rosen

1,120

67 Comments

This article highlights the exciting strides of AlphaFold3 in predicting protein structures, revolutionizing medicine. At Rejuve.Bio, leveraging such AI advancements could accelerate our understanding of cellular mechanisms, enhancing precision in therapeutic interventions. What's next? Learn more about Rejuve.Bio and our crowdfund here bit.ly/rjvbcrowdfund https://lnkd.in/gYFarUEZ

4

Regeneron is expanding its genetic medicine efforts and will work with California startup Mammoth Biosciences on gene-editing programs reaching parts of the human body beyond the liver, the companies announced Thursday.... ...Under the deal terms, Regeneron will pay $5 million and make a $95 million upfront equity investment in Mammoth, with the startup eligible for up to $370 million in milestone payments and potential royalties for each target.... #CRISPR #geneediting #cellandgenetherapy #advancedtherapies #lifesciences #biotech #biotechnology #equityinvestment #investment #funding #financing #milestonepayments Jennifer Doudna Lucas Harrington Christos Kyratsous Trevor Martin #delivery #royalties #innovation #advancingmedicine

67

1 Comment

Interesting in-depth blog post on PacBio challenges by Keith Robison, well worth a read. My view is broadly similar. Stock is now down 6X since I made my 2024 prediction: (https://lnkd.in/gecsqHTe): "PacBio - Tough spot as again LR market is limited and Oxford Nanopore Technologies is coming at them from below with less expensive instruments so it'll be a battle over a small patch of ground. Hence PacBio buying Omniome, but not clear that it has a SR value proposition that can compete with Illumina (and Element Biosciences)." As Keith points out it's hard to see an M&A deal that would work here even at this low price. IMO private equity isn't going to be interested as they look for good growth potential and that's not showing up; Keith suggests Thermo as a buyer - an interesting idea as they have a decent onco business around Ion Torrent; PACB would give them a more scalable SR technology for liquid biopsy and LR *might* be nice for onco too. Hmmm. Maybe Element or Ultima would be a better fit for them...and much less complex a deal.

48

Morning everyone! Today's blog explores how scientists are using an AI method called deep learning to crack the code of enhancers. Enhancers are small sequences of DNA that don't code for proteins, but do control expression of a gene sequence (sometimes from very far away). This new deep learning method is making it easier to open doors for researchers, and design patient (and cell-specific) therapies by manipulating gene expression. #bioinformatics #celltherapy #deeplearning #AI

6

A new company called Xaira Therapeutics just launched with over $1B+ billion in funding for using AI in drug discovery R&D. To give you some context, the last time we saw this level of fundraising was for Roivant Sciences, which focuses on creating companies around abandoned drugs, and Altos Labs, with $3B for cellular rejuvenation programming. But this is the 1st for an AI drug discovery R&D company. Interestingly, a significant portion of the company's technology originates from the Institute for Protein Design at the University of Washington, which is renowned for its work in protein science. This institute is led by Prof. David Baker, the co-founder of this and also the Charm Therapeutics. Read the full story here: https://lnkd.in/eCZfV4CW #drugdiscovery #artificialintelligence

14

1 Comment

Great post by Hugo Villanueva, Ph.D. and one that stimulated a lot of debate. Clearly our sector needs more effective tools for discovering and developing new therapeutics that achieve improved clinical development success rates. However, it’s not just about the technologies. Data driven decision making embedded in business models like the one we operate at Cumulus Oncology mean only the best assets are moved forward at every stage. Completely agree with Hugo’s point about the need for in vitro and in vivo validation of any output from the array of platforms at our disposal. Until we improve success rates in clinical development, the value of a given platform cannot truly be validated. Here’s hoping techbio coupled with evolving business models can move the dial on clinical success. That’s a meaningful outcome from all the hard work and investment.

20

Intellia Therapeutics, Inc. Therapeutics (NASDAQ: NTLA) made significant strides with its #CRISPR-based gene therapy, NTLA-2002, as positive long-term data from a Phase 1 study in hereditary angioedema (HAE) led to a 13% jump in stock value. The data, presented at the European Academy of Allergy and Clinical Immunology - EAACI Congress 2024, showed a remarkable 98% mean reduction in the monthly attack rate after a single dose, with over 20 months of follow-up. Impressively, 80% of patients remained attack-free, including those with the most severe cases. Anticipating topline Phase 2 results mid-year, Intellia aims to initiate a pivotal Phase 3 study in the latter half of 2024, pending regulatory feedback. #genetherapy #cellandgenetherapy #advancedtherapies #biotech #biotechnology #lifescience #lifesciences #longtermdata #patients #progress #HAE #functionalcure #groundbreakingtreatment #positivesafetyprofile #clinicaltrials #patientdata

70

Synthetic Biology is a truly disruptive technology. It is the artistic engineering of biology, achieving feats that might not have previously seemed possible. Here are three interesting examples of companies using Synthetic Biology to disrupt industries. Capra Biosciences has revolutionized chemical production using synthetic biology. Co-founders Elizabeth Onderko and Andrew Magyar discovered a way to repurpose biofilm to create retinol, a powerful anti-aging ingredient, at a fraction of the cost. Biofilm is an aggregate of microorganisms that adhere to surfaces, often responsible for infections. The process they use occurs in a bioreactor, a system engineered for developing biological mass. Their technology could impact industries such as industrial lubricants, personal care, aviation, aerospace, and electric vehicles. Ergbio uses innovative fermentation processes to manipulate biology and produce incredible outcomes. Imagine a world where agricultural waste and leftover wood chips can be transformed into aviation fuel. This company, led by founder Vineet Rajgarhia, who pioneered PLA bioplastics at Cargill and holds patents for polylactic acid (A type of plastic made often from sugarcane and corn), is turning this vision into reality. As these trends progress, and are supported with sound market strategies and adequate funding, these groundbreaking technologies have the potential to challenge traditional fossil fuel industries and contribute significantly to a more sustainable world. Kraig Biocraft Laboratories, Inc. modifies the DNA of silkworms to make spider silk. Spider silk is a remarkable and strong biological product. Though much lighter than steel, it has a stronger strength-to-density ratio. When I spoke to Jon Rice, COO, he told me that their silk products have applications in military, industrial, and consumer markets. Their product is in high demand; the company is profitable and even publicly traded (OTCQB: KBLB). These companies are great examples of the disruptive potential of synthetic biology. At Fruitionary, we spotlight groundbreaking innovations through our exclusive articles. If your startup is pushing the boundaries in this field, reach out to me at ali.darwish@fruitionary.com.

16

Announcing: AgingBiotech.info /therapeutics (direct link: https://lnkd.in/gRk_J7bP) a new (beta version) table attempting to list most (potentially) therapeutic interventions against aging that are already available, primarily supplements & already-approved drugs but also including lifestyle factors & other categories (eg environmental interventions). The goal is not to pass judgement on whether each works or to rank them all comprehensively but rather to take each & summarize several ways to evaluate it that others have already put forward plus links to as many useful sources for more info as easy to include. I'm launching this without it being comprehensively filled out on the assumption that it's better to release the substantial info already collected since many of the purported therapeutics are commonly discussed & even commonly used already, but in many cases by people who have not looked at very many sources of info about them. Many people are experimenting with personal use & some doctors are recommending some of these aging interventions despite that scientific understanding of many is woefully incomplete. What data & analysis exists is not easy to collect---there's no central place to quickly find links to much of the relevant papers & data. This table is meant to be an initial effort to be one such place, to be a jumping off point to allow people & doctors to quickly find many relevant papers & results for any given therapeutic commonly discussed as an aging/longevity intervention. The overall philosophy of this website is that amazing things are coming based on technologies in development but not yet available and based on science not even yet worked out in academia (& so not yet even in biotech development). Understandably, some people do not want to wait, but one should be cautious about over-interpreting early data on drugs & supplements w.r.t. longevity. This table is meant mostly as a way to aid deep dives to educate on the full extent of data available. This is basically a bunch of jumping off points meant to be more helpful to peruse first before just typing one version of the name of some therapeutic into Google. This is absolutely not a recommended "stack", nor a direct endorsement. FWIW, my own personal sense is that almost all the drugs & supplements here don't have enough evidence yet for most people to adopt them (especially to try to achieve super-physiological levels) and that by far the most important column is the who-needs-it column called "best diagnostics/biomarkers to determine individual need & to titrate dose", for which there are woefully inadequate answers for most things. I think a lot of people overestimate how much good many supplement or drug molecules will do & simultaneously my sense is that the lifestyle stuff is woefully underestimated & underutilized, & mostly safer. Hope this is useful to some people. Those who want to help fill in the missing details should reach out directly.

108

17 Comments

In 2022 when Illumina and GRAIL leadership where touting how many lives would be saved if only the antitrust authorities got out of the way, here's what was really happening. Please read carefully, shows how this "life saving" test doesn't work: "[With the] San Francisco firefighters, the test did not identify the statistically expected number of cancers, provided false positives for half the cancers it did identify, and missed at least three cases of confirmed cancer. In other words, the exercise showed Galleri to be a disaster." "In this example prominently featured on GRAIL’s website and in marketing materials as an example of how “multi-cancer early detection screening can be critical for those at elevated cancer risk”—GRAIL provided 1,786 screenings to a group of San Francisco firefighters and their family members, a “high risk” group for certain kinds of cancer. During that testing round, which was conducted on December 6, 2022—Galleri generated six false positives and identified only five instances of cancer." "...such a result is alarming in light of the fact that, based on statistical experience, cancer should have been detected in about 29 (not five) of the 1,786 tests. Moreover, of the five instances of where cancer signals were identified, two individuals already knew they had cancer to begin with. Further, all of the instances of detected cancer were at a “late stage,” and where the cancer was too advanced to make a difference for the patients. One firefighter was diagnosed with stage 3 pancreatic cancer and is now in hospice, while another firefighter was diagnosed with lung cancer, which has now metastasized to the brain." "Galleri also missed at least six instances in which the San Francisco firefighters actually had cancer—failing to identify instances of melanoma, prostate cancer, and lymphoma that were identified by private doctors just months after the Galleri test indicated “no cancer signal.” "Further, in one instance in the San Francisco firefighters screening where Galleri generated a false positive, the patient underwent a painful bone marrow biopsy procedure to determine whether the patient did have cancer. In that case, the patient’s bone marrow biopsy procedure, clinically shown to involve “unbearable pain” to the “worst possible pain” a patient can experience, revealed that there was, in fact, no cancer." "The screenings provided to the San Francisco firefighters were an expensive “disappointment.” According to Tony Stefani, the organization’s founder, the screenings demonstrated that the probability of catching an early-stage cancer through the Galleri test was “negligible,” and the screenings only caught “some serious cancers at a later stage,” which likely would have been detected within one or two months without the test. Given the test’s high costs and useless real-world performance, Stefani stated that Galleri was a total “disappointment” and that the foundation had been sold a “bill of goods.” 🤯🤯🤯

106

14 Comments

A lot of new functionality in the last month.

21

I'm CEO of Tierra Biosciences, a protein engineering and production company in the Bay Area, California. Always looking for the best new advice, I asked ChatGPT the question: What does the future of making proteins with cell-free technology hold? ChatGPT's Answer: The future of protein production using cell-free technology is filled with transformative potential and several exciting advancements: Rapid Production: Cell-free systems can synthesize proteins much faster than traditional cell-based methods. This speed is crucial for accelerating drug development and production. High-Throughput Screening: Cell-free technology enables the rapid synthesis and testing of large libraries of proteins. This capability is invaluable for the quick identification and optimization of potential therapeutic candidates. Customization and Flexibility: Cell-free systems offer precise control over the synthesis environment, making it easier to produce complex proteins and conduct specific modifications that might be challenging in living cells. This flexibility is critical for designing proteins with specific functions or properties Integration with Computational Models: Combining cell-free protein synthesis with computational models, including machine learning and large language models (LLMs), can optimize production processes and predict protein behavior with greater accuracy. This synergy can accelerate the development of new proteins and therapeutic molecules. Exploration of Novel Proteins: Cell-free systems allow for the exploration and production of proteins from organisms that are difficult or impossible to culture. This can lead to the discovery of novel proteins with unique and valuable properties.   ChatGPT’s answer aligns perfectly with what we are doing at Tierra Biosciences, and the Cell-Free + AI/LLM solution we are unveiling at the BIO meeting in San Diego - The Tierra Flywheel. The Flywheel is a fusion of our combinatorial cell-free protein synthesis with a powerful generative AI model to massively accelerate therapeutics discovery and development to the clinic. I am looking forward to engaging with Tierra Biosciences partners and future collaborators at BIO in San Diego! #TierraBiosciences #BIO2024 #AI #Protein #Therapeutics #ChatGPT   Please send me a note or look me up on the BIO partnering platform to learn more.

81

1 Comment

Inside the XBI Index: The S&P Biotechnology Select Industry Index (XBI) tracks the performance of biotech companies, using a modified equal-weight methodology. It includes firms from early-stage startups to established biopharma, focusing on innovative fields like gene therapy and oncology. While it offers diversified exposure and potentially high returns, it also carries risks due to industry volatility and market sentiment impacts. #Biotech #Investment #XBI #Nabil_Alhakamy #pharma https://lnkd.in/dc-AUFNj

15

1 Comment