Rafal Pielak

The last few days I've been attending SynBioBeta conference in San Jose, CA. Really cool innovations that are tackling big problems in health, industrial production, and climate. It was also AgFunder's AGM... some non-standard observations: 1- Venture markets are not back: it will not be a bounce, but a slow recovery 2- Smart startups are partnering with engineering/EPC firms earlier in their life. This is key to de-risk scale production from day 1. My first employer out of college Black & Veatch was a key partner in the growth of Tesla, and now they're active in the bio space 3- If you say you're AI, you better prove it. Nothing wrong with saying you're doing ML

15

118 VCs (one hundred eighteen!) are gathering in San Diego next week - to meet with 30 SD startups. But it's so MUCH bigger than just those 30 co's. It brings VCs back - when they see quality companies. It helps those who are next-in-line and adjacent. It enables us to send deal flow all year 'round. It attracts talent and other companies. It inspires entrepreneurship. Connect is working for SD. Together, we're building the best damn innovation ecosystem on the planet. Year over year. Five.Ten.Thirty.

264

25 Comments

The FDA greenlighted one of our portfolio companies to move a novel antidepressant drug to Phase 2a clinical trial! I am excited to share important positive news from Freedom Biosciences, a San Francisco-based clinical-stage biotech we have invested in via LongeVC back in 2023. The company has just announced FDA approval of investigational new drug (IND) application for their FREE001 Phase 2a program in patients with treatment-resistant depression (TRD). Freedom Bio plans to initiate its Phase 2a clinical trial in the first half of this year, which has the potential to address a critical unmet medical need in patients suffering from TRD. FREE001 is a ketamine-based combination therapy for the treatment of TRD, which builds on John Krystal work in Yale University. He showed that the combination may extend the antidepressant effects of ketamine from 2-7 days up to 2 to 3 weeks. Major depressive disorder (MDD) is a debilitating and chronic condition with limited effective treatment options, and Freedom Bio tries to tackle its specific case, treatment-resistant depression, when a person diagnosed with MDD does not respond adequately to a course of appropriate antidepressant medication within a certain time frame. MDD is one of the most common mental health disorders in the United States (US), with an estimated 21.0 million adults (8.3% of all adults) having at least 1 major depressive episode in 2020 (link to statistics in the comments). MDD also impacts physical health, worsens outcomes of other medical conditions, and, on average, results in a 10-year reduction in life expectancy. I am inspired by the achievements of Dina Burkitbayeva and Freedom Bio’s team in this truly challenging and notoriously hard area of drug discovery! Way to go, folks. #neuroscience #drugdiscovery #FDA

89

6 Comments

Excited to have led the closing panel entitled "Bridging Science and Investment" in San Diego, CA. Joined by Dr. Sanjeev Thohan (Cogentis Therapeutics, Inc./Phoenix Molecular Designs) and Dr. Yuhua Ji (Grace Science, LLC ), we explored the intersection of scientific innovation and investment strategies. Key topics of this thought-provoking panel included: - Strategic investment approaches in the evolving biotech landscape - The critical role of venture capital in accelerating drug discovery - Innovative funding models for cutting-edge pharmaceutical research - The future of biotechnologies and the investment opportunities they present Thank you to the panelists for sharing their invaluable insights. Our discussion underscored the vital role of strategic investments in driving innovation and shaping the future of drug discovery and development. Together, we are paving the way for groundbreaking advancements in biotech. #biotechnology #MedicinalChemistry, #strategy #drugdevelopment Proventa International #Bio2024 BIO International Convention #DrugDiscovery #Investment #VentureCapital #Biotech #SanDiego American Association for Precision Medicine (AAPM) WISE World Investors & Entrepreneurs Society Agility Pharmaceuticals Precision BioPharma #ai #news

35

2 Comments

Working with Ksenia Burka and Giorgio Fracassoover the past six months was a pleasure. Delivery of genomic medicine is an important thesis area for us, and Reactosome opens up a new vector in this space. Reactosome's breakthrough is a Synthetic Nucleus, which mimics the functions of a cell nucleus, carrying with it a DNA/RNA payload and packaged enzymes to continuously and controllably express cargo sizes that existing methods cannot deliver. The company is looking for industry partners and pharma advisors as they advance the platform. Recommendations will be appreciated! One last thing, it was wild learning that this approach is inspired by Giorgio Fracasso's study of the origin of life. To study how life comes together he modeled life bottom-up with cell-free synbio methods - modeling how artificial cells can come together and operate as a system. Studying these complex and dynamic biological systems warrants one learn and work with biological noise and variability - building in many layers of control and tunability - something Reactosome's tech does exceptionally well. #synbio #demo-day #indiebio #series-seed #life-sciences

19

3D printing is having a breakout moment, turning its long held promise into a reality that is arriving at pace and at scale. Over the next 5 years: - Consumers will expect customized products at scale - Computers will surpass human creativity and skill in product design - New infrastructure is needed to protect IP if anything can be printed anywhere  - Global supply chains will be meaningfully dismantled as products get printed at their point of sale I sat down with Philip DeSimone, Co-founder of Carbon, the most advanced 3D printing company already operating at scale serving customers in 17 countries ranging from Adidas to Ford. With over 300 patents filed, Carbon has raised $680M from the likes of Sequoia, Temasek, and Google. Check out 5YF Episode #14: 3D printing breakthroughs, AI designed products, mass customization, spare body parts, dismantling global trade, IP piracy, and the future of production w/ Carbon Co-founder Philip DeSimone https://pod.fo/e/234185 #3Dprinting

9

3 Comments

🌟Innovative VC Firm Overcomes Exits Drought with Secondary Sales🌟 ⛵Navigating a challenging landscape where exits are scarce, Santa Barbara Venture Partners (SBVP) has pioneered a novel approach to sustain its growth and attract investors for its second fund: secondary sales. Instead of waiting for traditional exits like IPOs or acquisitions, SBVP opted to sell shares of its portfolio companies, demonstrating its ability to generate returns for investors and stand out in a competitive market. 🎤According to Dan Engel, founder and managing partner of SBVP, these secondary transactions have been a game-changer, sparking investor interest and bolstering the firm's credibility. By leveraging its recent successes, including a lucrative stake in sports-betting company DraftKings Inc.' acquisition of digital lottery app Jackpocket, SBVP seized the opportunity to return profits to its limited partners (LPs) and pave the way for its second fund. 💡Engel highlighted the challenges faced by young VC firms in raising subsequent funds, particularly amid a downturn in exit activity and heightened investor scrutiny. With traditional exit routes becoming increasingly elusive, the pressure is on for firms to demonstrate tangible returns and establish a track record of success. ✨"For us, secondary sales have been a game-changer. They've helped us return profits to our LPs and attract investors for our second fund," said Dan Engel. 💰For SBVP, the decision to pursue secondary sales was driven by the need to provide liquidity to LPs and validate its investment thesis in the eyes of prospective investors. By strategically offloading portions of its holdings in high-performing portfolio companies like Bark Technologies and Rad AI, SBVP not only generated substantial returns but also bolstered investor confidence in its ability to deliver results. ⚠Despite the complexities and potential stigma associated with early share sales, Engel emphasized the importance of prioritizing investor returns and seizing opportunities to unlock value for stakeholders. With a focus on profitability and transparency, SBVP remains committed to its mission of delivering sustainable growth and maximizing returns for its LPs. 🔍 "Returning profits to our investors is our top priority. By strategically selling shares, we're proving our commitment to delivering results and driving value for our stakeholders," added Engel. As SBVP continues to explore secondary transactions and expand its investor base, the firm stands as a testament to innovation and resilience in the face of market challenges. 🚀 ✅ Looking to raise capital for your #fund and increase the international pool of your LP #investors?   🤝 Need warm #LP introductions?   📝 Selling #secondaries to increase liquidity?   🧐 Looking for co-investments?   ▶ G+QUANT's link for inquiries and fund decks: https://lnkd.in/gjC_EuTE #VCInnovation #SecondarySalesSuccess #InvestorReturns #ValueCreation 

2

Looking back at the past 30 years, I remember myself doing science about 55-60 hours a week, and then helping venture capitalists and biotech start-ups about 70-80 h/week. Usually unsatisfied, sometimes exhausted, but pleased overall. This overexciting workaholism was somehow interrupted last year. I had less work and a lot of mountaineering, - climbed about 5.5 Chomolungma attitudes during the year. It feels like I have reached the stage at which it is a time to start sharing experiences and understanding of the universe. This week, I started to share by publishing an analytic report at SeekigAlpha about TG Therapeutics. This small biotech company has developed a third-to-market anti-CD20 mAb for the treatment of multiple sclerosis (MS). Along with the company, this report briefly touches upon current treatments for MS, the competitive landscape of therapeutics, and the uncertainties surrounding the development of new BTK inhibitors. https://lnkd.in/drAFx9vt

10

This analysis, at least anecdotally makes sense to me. In many situations, infringe and holdout is the least painful option for large infringers. The system enables it. - The plaintiff must allocate the time and $$ to assert, taking time and $$ away from selling and developing products. Even if they engage litigation financiers they are limiting their upside potential. - The infringer continues to infringe while employing stall tactics or simply relying on the painfully slow, overburdened legal system. - The cost benefit analysis for infringers - "infringe and pay lawyers" typically outweighs the cost of design around or license. - Enhanced damages and injunctions are rare. - Litigation insurance products reduce risk all around. "The Marcum report shows that there is indeed something wrong with the patent system in the United States but it’s not excessive litigation or patent trolls. The real problem is the inability of patent owners to enforce their rights against infringers. Given the difficulty of obtaining injunctive relief and the limited enhancement of damages, it is unsurprising that predatory infringement has become a standard business practice when, at worst, all an infringer can be expected to pay is a reasonable royalty and, at best, nothing at all."

5

 📣Join Our Mission: Women's Health! Despite recent growth in the women’s health space, there is still unmet demand for products and services. Menopause has been a particularly overlooked segment of the market: only 5 percent of FemTech start-ups address menopause needs globally (McKinsey & Company, 2024). Nevertheless, the acceleration of advances in women’s healthcare holds considerable implications for investors and stakeholders across the value chain and beyond. At KRING, we're pioneering innovative solutions in women's health, focusing on cognitive health, sleep management, menopause, fertility, and more - with Menopause, an active health challenge we are currently exploring. While diving into Validation, our concept has garnered significant interest across the health innovation ecosystem, corporate partners, and investors. ✅ Chief Commercial Officer (Co-founder) We're seeking dynamic Commercial Co-founders with robust entrepreneurial backgrounds with experience of scratch to commercialization, and exceptional leadership skills. Experience in negotiating complex agreements is advantageous, but a passion for women's health is essential. https://lnkd.in/dVRwJ6i8 ✅ Menopause Expert: Chief Product Officer (Co-founder) We're looking for a scientific expert with a deep understanding of medical science, clinical research, and regulatory requirements, to lead the development of innovative healthcare solutions for women's health. https://lnkd.in/dXX3RWQY 🧠 The Concept: Building a Digital Platform for Women's Health Our digital platform helps women tackle midlife challenges, including menopause, by enhancing sleep quality, addressing weight gain, and boosting self-confidence. Components include data gathering, tailored recommendations, personalized wellness programs, and a supportive community. 📍Join Us in Copenhagen Our team is headquartered in Copenhagen, offering an exciting opportunity for individuals based in these cities or open to relocation. If you're intrigued by this opportunity, we'd love to hear from you. Reach out to Marina Miteva and Agnes A. to learn more. Join Entrepreneurs, Innovators, and Investors like Britt Meelby Jensen, Kristine Leerbeck, Christina Høgh Selmer Kirk, Anne Mette Bang, Benjamin Suhr, Anja Monrad, Sonal Pendharkar Kulkarni, Ella Smoraczewska Harris, Fanny Hauterat, Sumeya Hassan, Rosemarie Wedell-Wedellsborg, Jane Kudsk, Susanne Brønnum, Pernille Foss, Sara Maria Franch-Mærkedahl, Gitte Nipper, Jenny-Ann Axson Johnson, and more in revolutionizing healthcare and shaping the future of women's health. Apply now.

41

4 Comments

Turn Biotechnologies, one of our portfolio companies, inked a $300m epigenetic reprogramming deal with Korean pharma giant (news in the comment). Founded in 2018 as a spinout from Stanford University, Turn Bio develops epigenetic reprogramming technology aiming to restore optimal gene expression and promote tissue regeneration by tackling aging effects in the epigenome. To achieve that, the company uses a specific cocktail of mRNA transcription factors. In its exclusive global licensing agreement with Korean pharma giant HanAll Biopharma, Turn Bio’s role is to develop multiple epigenetic reprogramming treatments for age-related eye and ear conditions. Ever since LongeVC investment in Turn Bio back in 2022, I’ve been watching the space of RNA therapeutics with interest. I think one of the most important aspects of Turn Bio is eTurna™ delivery platform, addressing the challenge of delivering RNA-based treatments. Delivery is a pain point in all RNA therapeutics. eTurna™ platform is customizable for different types of cargoes and routes of administration, using ionizable lipids that are safer and clear the body quickly. It reduces immunogenicity and enhances delivery efficiency. As Turn Bio co-founder Vittorio Sebastiano said, the power of the company’s technology is its ability to “rejuvenate cells in virtually any organ in the body.” Recently, Turn Bio also received positive feedback from the FDA during an INTERACT meeting regarding their skin rejuvenation therapy, TRN-001 (link in the comments). This puts the company on track to become the first longevity biotech to take cell rejuvenation therapy to clinic! #mRNA #rejuvenation #longevity #agingresearch Image credit: Longevity.Technology

89

5 Comments

I'm so excited to continue supporting Prolific Machines, Inc., and the incredible Deniz Kent, PhD ,Max Huisman, and Declan Jones. Today's cellular biology processes are incredibly expensive, inefficient, imprecise, and sometimes purely ineffective. These processes are used from everything from making antibodies to treat diseases, to fermentation used to make high-value nutritional proteins in baby formula, to whole cuts of cultured meat. Prolific has developed a biology platform that leverages light to guide cell behavior and optimize performance over time using AI. By combining light, bioengineering, hardware, and AI in fundamentally new ways, Prolific can help pharmaceutical, nutritional, and therapeutics companies get to market faster, less expensively, and more efficiently — ultimately in hopes of helping improve outcomes — a mission any of us can get behind. Mark Cuban Peter T. Frederick Blackford Cooper Rinzler David Adelman Darco Capital Breakthrough Energy Michael Schulson Kevin Love Tobias Harris Breyer Capital Charles Besser Brennan Besser Lettuce Entertain You Restaurants https://lnkd.in/ea2TqdQk

158

17 Comments

On the latest Vital Signs, Nikhil Krishnan and I had a ton of fun chatting with Dr. Atul Butte. Dr. Butte is a professor at UCSF, Chief Data Scientist of the UC Health System, and a co-founder of numerous healthcare startups. In our conversation, Dr. Butte shared his takes on healthcare AI opportunities, challenges, hype, and more. A few highlights: ⚡LLM use cases, data, and growth LLMs are already helping to solve the “drudgery” aspects of medicine, such as automatically drafting SOAP notes and patient messages. Dr. Butte is excited about future applications of LLMs that can help with the “cognitive” aspects: with difficult medical problems an LLM might be able to stitch together disparate pieces of information to generate a potentially novel solution. He also highlights that prompt engineering will become the next “coding language” as so much of leveraging LLMs is knowing how to ask them the right questions. Additionally, Dr. Butte discusses how since 2016, UCSF has been working to deidentify its patient notes so that it can query them to answer clinical questions and ultimately enhance patient care. ⚡The need for patient-facing AI As patients are increasingly able to access their own personal health data in nicely structured formats (e.g., EHRs, wearables), they desperately need more tools to help them interpret and make decisions using that data. Dr. Butte understands that these patient-facing solutions are challenging to get funded but he emphasizes that patients need to receive the benefits of AI sooner. ⚡Evaluating healthcare AI solutions In order to evaluate AI solutions, we often put human specialists – such as medical professionals – on the same tasks. Understanding that specialists often disagree with each other, a significant challenge arises in figuring out how we can evaluate AI considering we can’t just “average” all the specialist opinions. Dr. Butte points out that there still remains a massive gap in AI evaluation tools. Additionally, there are so many organizations that want to have a say in how healthcare AI is regulated that the landscape is uncertain. An awesome conversation with an expert on all things AI meets healthcare. Listen to the full episode below: Spotify: https://spoti.fi/3Wr3643 Apple: https://apple.co/4acwgan

82

8 Comments

It was very fun to develop this AI judge for Climatech's Great Global Innovation Challenge and see it in action. Research has demonstrated that "Data-driven initiatives have been shown to help VC firms reduce gender bias and make better, fairer investment decisions" (https://lnkd.in/g2afQDnv / https://lnkd.in/gDnf4att). Additionally, "Machine learning models have already been proven to outperform human investors in deal screening" (https://lnkd.in/g2afQDnv / https://lnkd.in/gwGAmbET), helping to identify high-potential startups more effectively. By incorporating AI into our evaluation process, we aimed to ensure a more equitable and objective selection of startups. Thanks Tod Hynes Daniela G. Alejandro Sevilla Russ W. ClimaTech Live for the great collaboration. #climate #AI #climatechange #startups #startupcompetition

11

According to the latest Pitchbook data, venture creation in biotech hit its slowest quarterly pace in eight years during 1Q 2024. With just over 60 new biotechs raising their first round of financing, the sector’s company formation activity has slowed 50-60% from its historic peak in 2021. Thank you Bruce Booth for penning your views on why this is a good thing. -Contraction in venture creation IS a healthy dynamic for the sector. -We need to ensure that the best ideas are getting advanced by the sector. -Greater discipline should translate into better returns in the long term for LPs and GPs/ VC #Venturecapital #Startups

25

2 Comments

Fascinating Low Valuation on IPA Therapeutics(NASDAQ:IPA $1.26) On March 29, 2022 IPA paid $20 million euros or approximately $22 million USD for BioStrand AI. The euro was trading(1 euro = 1.10 USD) at this time. Since this acquisition BioStrand AI has announced several significant events/successes including, granting of the HYFT Technology Patent by the European Patent Office(EPO), BioStrand solves the Information Integration Dilemma(IID), BioStrand creates a revolutionary approach to biological sequence retrieval, BioStrand introduces an advanced Foundational AI Model utilizing LLM stacking & HYFT Technology, InterSystems & BioStrand AI Collaborate to Unveil Innovative Integration of Vector Search, BioStrand's AI has been learning from IPA's leading, proprietary Antibody Discovery Database(possibly the best in the World)for the last 24 months, and much more. IPA has been working on antibody research for 40+ years. https://lnkd.in/gJHWdgck https://blog.biostrand.ai Yet, the entire current Market Capitalization of IPA(CRO + BioStrand + Talem) is approximately $35 million USD today. IPA's Contract Research Organization(CRO) has had 3 record revenue quarters in a row, is growing at approx. 20%, and Fiscal 2024 Revenue should be around $20 million USD. They deal with 19 of the top 20 pharmas, and have over 600 partners. One could argue that the CRO is worth between $80-$120 million. FairJourney Biologics(an excellent CRO) was just put up for sale for $1 Billion+. Although FJBio has $45 million in projected EBITA, IPA has better numbers regarding projects, libraries generated, partners, species used, and 1/2 the employees. In other words, better data to train the AI models. Wet lab combined with AI will be critical moving forward. I also believe BioStrand AI is undiscovered by most stock market participants. For Information Purposes Only. Please complete your own due diligence. CFP has a position in IPA. Is a short squeeze possible? Sum of the parts(1 + 1 = 11) IPA (ImmunoPrecise Antibodies)BioStrand (a subsidiary of IPA) InterSystems hashtag #ai hashtag #HYFTTechnology hashtag #drugdiscovery hashtag #LENSai hashtag #antibodies hashtag #LLMS hashtag #NLP hashtag #semantics hashtag #pharma hashtag #healthcare hashtag #biotech hashtag #multimodality

14

9 Comments

It's been great to get a first-row seat to Transition Biomining's evolution! Sasha Milshteyn walked into our offices for a casual meet & greet back in 2023, with just a notebook. He walked out of the meeting with a key fob to our offices and access to our labs, launching a stealth-mode build that would become Transition Bioming. haha! Copper is an entrenched industry, highly concentrated, and with an undeniably strong demand pull for the energy transition. The industry has to think hard about how to cater to demand at a time when ore quality is declining and mixed diverse mineralogies at mines prevent existing approaches to tap the reserves economically. Check out how Transition Biomining can make a dent with an asset-light approach that brings out the best in each heap of copper. Got to roll up my sleeves and made my first cameo with this video! Hope you enjoy it. https://lnkd.in/d6bD_r95 #copper #energytransiton #cleantech #climatetech #vc #seriesseed

40

1 Comment

Exciting news for startups! California accounts for about 50% of all venture investments. The not-so-secret reason is that non-competes are illegal in California, so engineers at FAANGs can build competitors without fear. Today, the US Federal Trade Commission declared non-compete agreements illegal nationwide. This means that engineers at big tech companies can now leave and build their own companies without fear of violating a non-competes (legacy agreements for executives are still enforceable - talk to your lawyer), this is a step in the right direction for fostering innovation and competition across the country. A variety of big-business groups have vowed to sue to bring non-competes back, but at least for now, they're gone! #startups #innovation #competition #noncompete Official Announcement: https://lnkd.in/gRXUpgDy Impending lawsuit: https://lnkd.in/gqSiVuTd

50

2 Comments

Thanks to advances in neuroscience, we now understand the brain chemistry driving #OperantConditioning-dopamine. We know dopamine releases are involved in drug use, gambling, compulsive behaviors associated with Internet use, and playing of video games. https://lnkd.in/gGvDjBe

13

1 Comment