Tag Archives: food

Advancing Early-Stage Drug Discovery with Mosaic Biosciences

12 Aug

By Caitlin Dolegowski, Marketing Manager, LSN

CaitiLife Science Nation is featuring Mosaic Biosciences, a returning RESI Boston sponsor dedicated to advancing early-stage drug discovery. Led by Chief Executive and Scientific Officer, Eric Furfine, Mosaic partners with biotech innovators to turn promising concepts into clinical candidates. In this interview, Eric shares how Mosaic’s experience and collaborative approach set them apart in moving ideas toward the clinic, and the types of partners they’re hoping to meet at RESI Boston.

Watch the interview:

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The Needle Issue #12

12 Aug
Juan-Carlos-Lopez
Juan Carlos Lopez		 Andy-Marshall
Andy Marshall

The Summer BIO report “The State of Emerging Biotech Companies: Investment, Deal, and Pipeline Trends” highlights how much China-based programs have contributed to the drug pipeline over the past 10 years.

A couple of weeks ago, Bloomberg also summarized deal data showing how the share of global licensing by Chinese biotech companies has jumped over the past two years.

Judging by a report listing 16 ‘high-value’ currently unlicensed assets from China being hawked by longtime Phalanx Investment Partners analyst David Maris, there is more licensing to come.

In this context, we read with interest a recent Science Immunology paper describing a monoclonal antibody (mAb) program targeting a novel phagocytic checkpoint under development at yet another Chinese biotech: MedimScience, founded in Hangzhou City in 2021. MedimScience is one of a growing cadre of companies, including LTZ Therapeutics, Dren Bio, Chengdu Kanghong, Antengene and ImmuneOnco, looking to develop novel myeloid cell engagers/phagocytic checkpoint inhibitors.

Phagocytic checkpoint inhibitors are drugs that circumvent the molecular cloaks that tumors throw around themselves to avoid uptake and destruction by myeloid cells, such as macrophages, monocytes, and neutrophils. The strategy first came to the fore through pioneering work on the ‘don’t eat me’ signal CD47, work carried out by Ravi Majeti and Irv Weissman at Stanford. Results from their preclinical studies spurred the launch of startup Forty Seven (subsequently acquired in 2020 by Gilead) and the first-in-class anti-CD47 IgG4 magrolimabprogram.Phase 1b trial results of magrolimab combined with azacitidine in acute myeloid leukemia (AML) patients were so impressive that, by 2022, more than 20 different companies had anti-CD47 programs in clinical development. This blew up spectacularly when early trials failed to be reproduced in larger efficacy trials of combinations — failure that was largely attributed to intolerability/anemia issues related to the target, slow action/early disease progression, and a failure to account for patient heterogeneity with regard to P53 mutation status. But the strategy is compelling and the hunt for new phagocytic checkpoints has continued with new antibody formats seeking to avoid these pitfalls.

Now, Cheng Zhong and his colleagues at MedimScience report the identification of a new evasion actor — PSGL-1 — that suppresses macrophage-mediated phagocytosis in a variety of hematological malignancies. PSGL-1, which was previously known largely for its role in cell adhesion, is highly expressed in various hematologic cancers, including AML, T-acute lymphoblastic leukemia (T-ALL) and multiple myeloma (MM).

Moreover, high PSGL-1 expression has been found to correlate with poor patient survival in AML, T-ALL and MM.

Using several mouse models, the researchers found that tumors lacking PSGL-1 show slower progression, increased macrophage infiltration, and higher rates of phagocytosis by macrophages, effects that were independent of T cells or dendritic cells.

Mechanistically, the team found that PSGL-1 disrupts the interaction between the cell-adhesion molecule ICAM-1 on tumor cells and the integrin LFA-1 (CD11a/CD18) on macrophages. And when they tested Novartis’ lifitegrast, an inhibitor of ICAM-1/LFA-1 binding, they found this largely abrogates the phagocytosis of PSGL-1 knockout tumor cells, confirming PSGL1’s role in impairing prophagocytic signaling and cytoskeletal reorganization required for effective tumor-cell engulfment.

The authors went on to develop a humanized mAb against PSGL-1 and show its ability to induce phagocytosis of human tumor cells in vitro and to reduce tumor burden in mouse models of AML, T-ALL, and MM. The antibody showed a good safety profile in non-human primates with no significant toxicity at high doses. Additionally, PSGL-1 blockade synergized with chemotherapy (doxorubicin) and antibody-based therapies (anti-CD47 and anti-CD38), further underscoring the translational potential of this strategy, particularly in treatment-resistant settings.

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Pullan’s Pieces #4 – China, Japan, Europe, Korea vs US- Collaborate or Compete?

5 Aug

As a deal maker, where should I go for a deal?  Where is my competition?

There is so much written about China, I thought I would try to put it in the context of other countries.

DEMOGRAPHICS:  China is Big but low GDP per capita, Japan has the oldest population.  Both Japan and China may have reached peak population, while the US has immigration to continue growth.  China and Japan have more big cities (making clinical trial recruitment easier).

The Medical Culture varies tremendously.  

The US, with the 3rd largest population and private insurance, has the biggest market

But there are even bigger differences in the magnitude of sales of new drugs. In the US, to be in the top 10 in 2031 means double digit billions.

The biggest company R&D budgets per company are in “Global companies”.

The biggest European and Japanese companies have become global companies. 

The biggest companies in the US have 45%-70% of their Rx sales in the US.

The biggest companies in Europe have 15%-30% of their Rx sales in Europe.

The biggest companies in Japan have <10% (Takeda) to 39% of their sales in Japan. (Smaller Japanese companies have most of their Rx sales in Japan)

The biggest Chinese companies have 80-95% of their sales in China.

2024 saw a surge in approvals: In 2024, China first-approved 93 innovative drugs, with 42% being domestically developed. But China is losing domestic market share to MNCs.

The biggest Korean companies with biologics (Samsung and Celltrion) have 10-20% of their sales in Korea.  The other big Korean companies have 70-90% of their Rx sales in Korea.

But China has almost as many drugs in Phase 1 thru 3 as the US, in almost as many companies as in the US.  

There are more companies getting series A in the US and in China but the dollar amount is smaller in China. 

The US leads in IPOs

But the Hong Kong Hang Seng Biotech Index was up 87% year to date (while the US XBI was down 6%).  

Europe is active in company acquisitions, but Asia is not.  

For companies with headquarters in the US, Europe, Japan and Korea:  most partnering deals are early and with more in-licensing than out-licensing. 

China does more out-licensing than in-licensing.  

So as a deal-maker, what do I think this data suggests?

1)  You need to capture value from the US, the biggest market and home of blockbusters.

2) US companies do the most in-licensing. US and Europe do the most M&A.

3) The most deals in 2024 and 1st Half of 2025 are still done at discovery and preclinical.

4) Japanese companies are increasingly global companies and do more in-licensing than out-licensing.

5)  China is a source of drugs to bring in, with many drugs in the pipeline and new series A companies needing partners to maximize their value. China does more out-licensing than in-licensing.  Presumably, the huge China vs China competition is pushing Chinese companies to innovate more to compete and to do deals.   And more exits (IPOs and M&A) encourages more VC funding of innovation.

6)  But the low cost and the high populations cities (for fast recruitment) means China should be considered for collaborations for your drug development.  (Just remember you need 20% of patients in the US for FDA approval).

7) Korea is a high-income market but small.  In-licensing deals are often early or at market stage.

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Pullan’s Pieces #3 – January – A Corner on Market Sentiments – Seed to Series A

29 Jul

As the saying goes, “What’s in a name? That which we call a Series A by any other name would smell as sweet.” Er… something like that, right? Hmmm, maybe it went a little bit differently.

But whatever it be, or not to be😊, the Seed Round is the new Series A. Clearly. I think we’ve all felt it for sometime but the data is in and the good ‘ole Series A just don’t buy what it used to. Nahhh… the Seed round does that, and it may buy more (equity) than it used to as a Series A (more data hunting and crunching required but one gets a sense that the venture capitalists are, well, capitalizing).

Labiotech does a really nice job collecting and summarizing a variety of topics related to financings and dealmaking in the biotech sector and the 2024 breakdown of funding offers the following approximations (roughly, with some rounding made by this author):

The internal breakdowns for amounts invested look like this:


Readers of this corner will know that we keep a close eye on the XBI

As usual, the outliers can skew the numbers (more on this in a moment) but the median amounts invested into these rounds puh-rihhhty much drive the nail in the coffin of the old thinking about Series dynamics. This data could be charted in another way in which an inverted bell curve would appear and a GAPING hole between $20M and $50M would stare back at you. Think about that for a moment… if you can’t get to value inflection for ~$15-20M, you better be raising $60-75M and have multiple reasons to do so as a cursory view of the companies listed in the dataset further indicates that the lower outliers (sub-median) on the Series A were generally geared for “finding out” about a single asset in the clinic.

Back to that previously mentioned outlier that can skew the averages… it also happens to bring even more of a spotlight to those famed words from Shakespeare which began this Corner on Market Sentiments. One of the companies in the 2024 data set raised a whopping $100,000,000 … as a Seed Round!! Indeed, a rose by any other name…

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MantaBio: RESI Boston Pitch Challenge Winner Shares What’s Next 

22 Jul

By Caitlin Dolegowski, Marketing Manager, LSN

CaitiMantaBio earned third place in the Innovator’s Pitch Challenge (IPC) at RESI Boston this past June, standing out among a competitive field of early-stage life science companies. In this interview, Co-Founder and President Carter Boisfontaine shares insights into the company’s fundraising efforts, their experience at RESI, and what’s ahead for the team.

Watch the interview:

Interested in pitching your company at RESI?

Applications are now open for the Innovator’s Pitch Challenge at RESI Boston, September 17, 2025. Selected companies receive full access to the conference, partnering meetings with investors, and exhibit space in the RESI Exhibition Hall. New! The September 2025 IPC Pitch Package now includes an optional second RESI pass at no additional cost, allowing an additional team member to attend and participate in partnering. Apply now!

Apply to Pitch at RESI Boston Sept. 2025

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The Needle Issue #11

22 Jul
Juan-Carlos-Lopez
Juan Carlos Lopez		 Andy-Marshall
Andy Marshall

Haystack chat

Molecular glue degraders (MGDs) are currently having a bit of a moment. In the first half of 2025, the number of papers describing such compounds has doubled.

2025 has also witnessed a whole raft of MGD startups publish research related to their programs:

Startup (location) Scientific founders (location) 2025 paper
Ambagon Therapeutics (Eindhoven, The Netherlands) Michelle Arkin (UCSF, San Francisco, CA), Luc Brunsveld and Christian Ottman (Eindhoven University of Technology) Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity
Cyrus Therapeutics (Seoul, South Korea) Keon Wook Kang (Seoul National University, Seoul, South Korea) High cereblon expression in neuroendocrine cancer confers vulnerability to GSPT1 molecular glue degrader
Matchpoint Therapeutics (Cambridge, MA) Nathanael Gray and Tinghu Zhang (Stanford University, Stanford, CA) and Edward Chouchani and Jianwei Che (Dana Farber, Boston, MA) Structure-guided design of a truncated heterobivalent chemical probe degrader of IRE1α
Monte Rosa Therapeutics (Boston, MA) Rajesh Chopra and Ian Collins (The Institute of Cancer Research and Cancer Research UK); Nicolas Thomä (Friedrich Miescher Institute, Basel, Switzerland) Structure-guided strategy for identifying human proteins predicted to be compatible with cereblon-based molecular glue degraders (see below for further details)
Oniria Therapeutics (Barcelona, Spain) Héctor G. Palmer, Esther Riambau, Isabel Puig, Josep Tabernero, Xavier Barril, and Carles Galdeano (Vall d’Hebron Institute of Oncology, University of Barcelona and ICREA) Cullin-RING ligase BioE3 reveals molecular-glue-induced neosubstrates and rewiring of the endogenous Cereblon ubiquitome
Proxygen (Vienna, Austria) Georg Winter (CeMM Research Center for Molecular Medicine, Vienna, Austria) Selective analysis of protein degradation by mass spectrometry enables degradome analysis and identification of direct protein substrates of molecular glues
Proteovant Therapeutics (King of Prussia, PA) Shaomeng Wang (University of Michigan, MI) Development of PVTX-405 as a potent and highly selective molecular glue degrader of IKZF2 for cancer immunotherapy
Sartar Therapeutics (Helsinki, Finland) Olli Kallioniemi and Harri Sihto (University of Helsinki, Finland) Pharmacokinetic profile and in vivo anticancer efficacy of anagrelide administered subcutaneously in rodents
SEED Therapeutics (King of Prussia, PA) Ning Zheng (University of Seattle, WA), Michele Pagano (New York University, NY) and Avram Hershko (Technion Institute of Technology, Haifa, Israel) UM171 glue co-opts CRL3 RING E3 ligase substrate coreceptor KBTBD4 as well as HDAC1/2, resulting in degradation of CoREST corepressors
Shenandoah Therapeutics (South San Francisco, CA) Jerry Crabtree and Nathanael Gray (Stanford University, Stanford, CA) A bivalent molecular glue linking lysine acetyltransferases to redirect p300 and CBP to activate programmed cell death genes normally repressed by the oncogenic driver, BCL6
Zenith Therapeutics (Basel, Switzerland) Daniel Nomura (UC Berkeley, CA); Nicolas Thomä (Friedrich Miescher Institute, Basel, Switzerland), and Martin Stahl (former Roche, LifeMine) Putative molecular glue niclosamide acts via ubiquitin E3 ligase CRL4AMBRA1-mediated degradation of cyclin D1 following mitochondrial membrane depolarization

On the commercial front, the march of startups receiving funding shows no sign of slowing down, with Trimtech Therapeutics and Booster Therapeutics raising substantive rounds. The first few months of the year have also seen the continuation of last year’s pharma MGD scramble to license programs from Triana Biomedicines and Neomorph, with deals based around molecular glues from Abbvie and Merck targeting Neomorph and Springworks, respectively.

In June, one of the flagship developers, Kymera Therapeutics, priced a $250.8 million follow-on offering (no mean feat in the present market) after announcing positive phase 1 safety data for KT-621, a novel MGD against STAT-6, and clinching a deal with Gilead Sciencesforanother small-molecule glue targeting cyclin-dependent kinase 2 (CDK2). All in all, we count 27 companies currently active in this preclinical space (Ambagon Therapeutics, Amphista Therapeutics, Booster Therapeutics, Captor Therapeutics, Cyrus Therapeutics, Degron Therapeutics, Dunad Therapeutics, F5 Therapeutics, Frontier Medicines, Lifemine Therapeutics, Magnet Biomedicine,Matchpoint Therapeutics, Montara Therapeutics, Monte Rosa Therapeutics, Neomorph, Oniria Therapeutics, Proxygen, Sartar Therapeutics, SEED Therapeutics, Shanghai Dage Biomedical Technology, Shenandoah Therapeutics, SK Biopharmaceuticals (Proteovant Therapeutics),Triana,Trimtech,Venquis Therapeutics, YDS Pharmatech, and Zenith Therapeutics). There are likely more.

Unlike their more recent cousins, the PROTACs (proteolysis targeting chimeras), MGDs have a long history. The archetypal MGD, thalidomide, was discovered back in the 1950s. From the late 1990s, a new generation of immunomodulatory imide drug (IMiD) derivatives of thalidomide were synthesized, culminating with the approvals of lenalidomide and pomalidomide for myeloma (which formed the basis for the Celgene (now BMS) franchise).

Unlike PROTACs, which use two ligands with a linker and tend to be rather unwieldy, MGDs are small, single compounds that induce conformational changes in E3 ubiquitin ligases and target proteins, reshaping both to enable binding. The vast majority of MGDs bind Cereblon (CRBN), leading to ubiquitination of the protein of interest and degradation in the 26S proteasome, although work is progressing to broaden MGD action to some of the other 600 or so E3 ubiquitin ligases (e.g., DCAF11,15 or 16, DDB1, SIAH, KEAP1, VHL, β-TrCP, Nedd1 and, just last week, TRIM21).

A key challenge in finding new MGDs has been a lack of understanding of the structural rules whereby MGDs turn their target proteins into CRBN ‘neosubstrates’, which has meant MGD ‘hit-finding’ is much more challenging, with fewer degrees of freedom than PROTACs.

What drug hunters have established is that many protein targets of glues contain a β-hairpin structural motif known as the ‘G-loop’. When a MGD brings a target together with CRBN, one end of the MGD interacts with a binding pocket in the C-terminal domain of CRBN, while the other end protrudes from the pocket and interacts with the G-loop (part of the so-called ‘degron’) in the neosubstrate. But how many proteins possess the β-hairpin G-loop or whether the loop is strictly necessary for MGD action have remained open questions. A recent study by Monte Rosa Therapeutics’ scientists starts to tackle these issues, disclosing a large cadre of potential new substrates for CRBN, some of which depart from the canonical β-hairpin G-loop, radically expanding MGD target space.

To map the full range of proteins potentially recruitable by CRBN through MGDs, the team led by John Castle and Sharon Townson developed computational algorithms to search for β-hairpin G-loop motifs in protein structures from two databases: Protein Data Bank and AlphaFold2. This approach resulted in 1424 candidate proteins, some of which were experimentally validated in MGD assays. The list included previously known neosubstrates, but also new proteins such as NEK7—a protein of interest as an autoimmunity target.

The researchers then wondered if the full β-hairpin structure of the G-loop is required for CRBN recognition and rescreened the structure databases looking for a minimal, structurally defined helical G-loop motif. This resulted in the identification of 184 additional potential neosubstrates, including mTOR, a well-established therapeutic target for drugs like rapamycin and sirolimus. Crystallographic data showed that the binding of this helical G-loop to CRBN is similar to that of the canonical β-hairpin G-loops.

As these protein–protein interactions have been well characterized, the team then tried to identify an even wider set of potential neosubstrates, looking now for proteins with sequences that might result in surfaces with electrostatic properties similar to known CRBN interactors, independently of secondary structure and the existence of G-loops. Using surface-matching algorithms, they identified and validated VAV1 (another autoimmune disease target) as a CRBN neosubstrate, providing compelling evidence that G-loops are not strictly necessary for the action of MGDs.

These findings show that CRBN recruitment through MGDs can be driven by a broader set of structural features than previously thought. The identification of a large number of neosubstrates potentially opens up a whole new set of previously ‘undruggable’ targets to MGDs (>1,600 proteins from many target classes, according to the Monte Rosa team).

The big questions, though, are still ahead. How will drug developers mitigate the risks of ‘off-tissue’ toxicity as this swathe of novel MGD compounds and new targets make their way into the clinic?One answer to the toxicity concern is molecular glue antibody conjugates (MACs), which can better localize glues to the tissue of interest. But that’s a subject for a whole other future Haystack Chat!

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Inomagen Therapeutics: RESI Boston June IPC Winner

15 Jul

Inomagen Therapeutics, led by Chief Business Officer Eric Sandberg, is working to redefine how atrial fibrillation is treated—starting at the molecular level. A recent winner in the Innovator’s Pitch Challenge at RESI Boston June. In this interview, Sandberg shares insights into the company’s novel approach, development progress, and how RESI helped build investor momentum.

Eric Sandberg
 CaitiCaitlin Dolegowski

Caitlin Dolegowski (CD): Tell us about Inomagen Therapeutics, what is your core focus, and what inspired your approach to treating atrial fibrillation?

Eric Sandberg (ES): Inomagen Therapeutics is a preclinical-stage biotechnology company developing a non-viral gene therapy to improve the treatment of atrial fibrillation (AF), the most common sustained heart rhythm disorder affecting 10M people in the US alone.  Patients with AF do not feel well and have a 4-5x increased risk of stroke, 2x risk of having a heart attack, and AF is a major cause of heart failure.  Unfortunately, current therapies, including cardiac ablation, have proven ineffective for many patients because they do not address the underlying mechanisms of the disease.

Inomagen’s approach is based on research conducted by our Founder, CEO and practicing electrophysiologist, Dr. Rishi Arora.  In his research laboratory, Dr. Arora identified major molecular mechanisms that contribute to AF in a majority of patients with AF; identified major trans-genes to selectively target these mechanisms in the atrium; utilized low energy electroporation to achieve therapeutic gene transfer and expression; and decreased AF in clinically relevant, large animal models of AF.

CD: What differentiates your platform from other therapies available to treat atrial fibrillation?

ES: Ablation is the mainstay of AF treatment. However, ablation success rates are suboptimal in patients with persistent AF. This is thought to be in large part because ablation is an anatomic procedure that is not targeted to the molecular mechanisms underlying AF. Inomagen has developed a non-viral gene therapy that targets one or more major molecular mechanisms underlying AF.  Specifically, we have demonstrated preclinical success delivering NOX2 shRNA plasmids to atrial tissue to achieve gene knockdown, to silence upstream mechanisms of AF, in order to achieve a therapeutic effect.  To be clear, our gene therapy is not replacing genes or editing genes, we are knocking down the expression of genes that are causing AF.  Based on our preclinical results, we believe that our gene therapy can potentially surpass cardiac ablation as the therapy of choice for atrial fibrillation.

To achieve safe and effective targeted gene delivery, we have developed a novel transvenous gene delivery system that uses low energy reversible electroporation to achieve high levels of gene transfection into atrial tissue.   We believe that our physical gene delivery approach overcomes the known challenges of using viral vectors which include insufficient gene transfection and well publicized off-target effects.  As such, we believe our gene delivery approach can potentially serve as a platform technology for other companies developing cardiac gene therapies, including gene therapy in the ventricles for congestive heart failure.

CD: Where are you in terms of preclinical or clinical development, and what are your near-term goals?

ES: With our recent development of a proprietary NOX2 shRNA gene plasmid and a gene delivery catheter, we have now achieved program readiness to initiate IND-enabling studies to gain FDA approval for a Phase I/IIa clinical study.  In the near term, we will be conducting IND-enabling studies in the 2nd half of the year in preparation for a pre-IND meeting with the FDA early next year prior to conducting pivotal tox and filing an IND in late 2026.  We aim to initiate our Phase I/IIa clinical study in 2027.

CD: What are you seeking in your current fundraising round, and what kind of investors or strategic partners are you hoping to connect with?

ES: We are currently raising a $5M Series Seed round and will be initiating a larger Series A round later this year to support the program through a Phase I/IIa study.  In the near term, ideal investors for Inomagen include angel groups and individuals, while we anticipate our Series A to be led by venture capital investors. Additionally, given the potential of Inomagen’s gene therapy to markedly improve the treatment of atrial fibrillation, we have several potential strategic partners who are tracking our progress.

Inomagen has multiple gene targets in our pipeline and a robust IP portfolio that includes 18 issued patents protecting genes/biologics and gene delivery.  We have an experienced team committed to bringing our gene therapy to the clinic.

CD: How did your participation in the Innovator’s Pitch Challenge at RESI Boston contribute to your visibility or investor outreach efforts?

ES: Our participation provided the opportunity to continue to share the progress that we are making with the attendees at RESI.  And being recognized as a top company in the Pitch Challenge has certainly provided increased visibility for Inomagen through Life Science Nation’s extensive readership.  We have experienced a further increase of interest in Inomagen, including a significant increase in traffic to our  website.

CD: Can you share any valuable feedback or connections that came out of the pitch sessions or RESI partnering meetings?

ES: Following our presentation in the Pitch Challenge, we added several more partnering meetings with interested investors. Given our experience at the June RESI meeting, we registered to attend the September RESI meeting as well.

CD: What advice would you give to fellow early-stage biotech founders about preparing for and participating in a RESI pitch competition?

ES: The RESI pitch competition provided a good opportunity to make sure that we are communicating the Inomagen opportunity clearly to potential investors. We appreciated the opportunity to join the many impressive companies presenting at RESI who have a passion to improve health care for patients and providers.

Applications are now open for the Innovator’s Pitch Challenge at RESI Boston this September.
New! The IPC Pitch Package now includes an optional second full RESI pass at no additional cost—bring a teammate to support investor meetings, pitch preparation, and maximize your conference presence.

Apply to Pitch at RESI Boston Sept. 2025

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