Drug Hunter

07/18/2025

Key Clinical Updates from June 2025 | https://drughunters.com/4nS8loN

In our recap of the clinical news from June 2025, we highlight the FDA approval of Gilead’s twice-yearly shot for HIV prevention and Nuvation Bio's ROS1 inhibitor for non-small cell lung cancer.

Our article also discusses Arvinas and Pfizer filing for approval for their estrogen receptor PROTAC, vepdegestrant; Altimmune reporting that its GLP-1/glucagon dual receptor agonist improved some measures of MASH in a Ph. 2 trial; and Schrödinger releasing initial Ph. 1 data for its MALT1 inhibitor.

Read it on Drug Hunter: https://drughunters.com/4nS8loN

07/18/2025

Sebetralstat Marks the First Oral and On-Demand Plasma Kallikrein Inhibitor Approval | https://drughunters.com/3IsZERA

KalVista’s plasma kallikrein inhibitor sebetralstat, has been approved as the first and only oral on-demand treatment for HAE (hereditary angioedema).

HAE attacks—severe and rapid swelling due to unchecked PKa (plasma kallikrein) activity—can be life-threatening for patients, and on-demand treatments were previously limited to injectables. In Ph. 3 trials, patients administered 300 mg sebetralstat after an HAE attack saw symptom relief begin at a median 1.6 h—5.1 h faster than the placebo.

Oral bioavailability of sebetralstat was solved during hit-to-lead optimization in part by a key swap from a benzamidine motif to a substituted pyridine ring, which dramatically increased solubility.

Read it on Drug Hunter: https://drughunters.com/3IsZERA

07/17/2025

📣 Reminder
Not a Hypothesis: The Free Drug Principle
https://drughunters.com/4kFubJj
Thursday, July 24th, 2025
8 AM PT / 11 AM ET / 5 PM CET

Join us for a thought-provoking Flash Talk with Dennis Smith, Drug Discovery Executive and former Vice President at Pfizer who will clarify common misunderstandings around the free drug concept.

Dennis will demonstrate why plasma protein binding and free fraction do not influence free drug concentration in vivo, challenging common assumptions in early drug discovery.

Don't miss this talk if you're looking to sharpen your skills in interpreting PK data and designing more effective drug candidates!

Sign-up here: https://drughunters.com/4kFubJj

07/17/2025

Small Molecules Unlock Big Opportunities in GLP-1R Drug Development | https://drughunters.com/458FXao

GLP-1R agonists have already transformed diabetes and obesity treatment—and are now being investigated in everything from addiction to neurodegenerative disease. While injectable peptides like semaglutide and tirzepatide dominate headlines, the next wave may come from chemistry: non-peptidic, orally available GLP-1R modulators.

In this article, we highlight notable clinical programs, from injectable peptides like semaglutide to oral small molecules like orforglipron, comparing their mechanisms, efficacy, and stage of development.

We also explore the rising therapeutic and commercial value of GLP-1R as a $150B+ target, and examine what may come next in this rapidly evolving space.

Read it on Drug Hunter: https://drughunters.com/458FXao

07/16/2025

We had a fantastic time reconnecting with familiar faces and welcoming new ones at our recent mixer in San Francisco!

A highlight of the evening was sharing Drug Hunter’s 2024 Molecules of the Year — with half of the nominated molecules having ties to the Bay Area. A perfect reminder of how collaborative and hands-on our discovery community really is.

Thank you to everyone who joined us—from early-stage startups to industry leaders. Stay tuned for future events!

Check out past events here: https://drughunters.com/40fZrHu

07/15/2025

Big Money Bets from June 2025 | https://drughunters.com/44NDWzb

In our June recap of biopharma deals, we highlight Sanofi acquiring Blueprint for $9.1B, Novo Nordisk partnering with Deep Apple Therapeutics on small molecule obesity drugs, BMS paying Philochem for a radiolabeled ACP3 ligand, and Gilead partnering with Kymera to develop oral CDK2 molecular glue degraders.

Read it on Drug Hunter: https://drughunters.com/44NDWzb

07/15/2025

Multi-functional ADCs for Cancer Therapy - FACT or FICTION?https://drughunters.com/44SAVgV
Thursday, August 14th, 2025
8 AM PT / 11 AM ET / 5 PM CET

Since the approval of the first ADC gemtuzumab ozogamicin in 2000, these precision medicines became available as treatment options in oncology indications. Yet, despite 466 ADCs advancing into clinical trials, only 14 have been approved, while many others have been discontinued due to several challenges, including limited target options, off-target toxicity, and developability risks.

In this Flash Talk, Jagath Junutula, President, CEO and Co-founder Aarvik Therapeutics Inc, will present the major factors driving ADC activity, ranging from target antigens, antibody-payload matching to linker design and conjugation methodologies.

He will also highlight the latest innovations in ADCs including multi-functionality, which aim to overcome the limitations of traditional ADCs and broaden their indications and effectiveness.

Don’t miss this opportunity to learn from past failures and discover how next-generation ADCs can overcome limitations of traditional ADCs.

Register here: https://drughunters.com/44SAVgV

07/14/2025

Can Brensocatib Open the Door for Neutrophil-Modulating Drugs? | https://drughunters.com/3GDlp0s

Brensocatib is an oral, reversible covalent, small molecule inhibitor of DPP1, currently under priority review by the FDA for the treatment of non-cystic fibrosis bronchiectasis—a severe, underdiagnosed chronic lung disease with no approved therapies.

With a PDUFA date set for August 12, 2025, brensocatib may soon become the first-ever approved DPP1 inhibitor, and the first drug to receive regulatory approval for this debilitating condition.

Discovered by AstraZeneca and acquired by Insmed in 2016, brensocatib’s success reflects a breakthrough in targeting neutrophil-driven inflammation without triggering immunosuppression or dose-limiting toxicities.

Its reversible covalent warhead was rationally designed to inhibit DPP1 with just the right level of engagement—enough to durably reduce activation of NSPs, but without completely shutting down the pathway.

If approved, brensocatib would not only address a major unmet medical need but also serve as a template for rational neutrophil-targeting drug design.

Read it on Drug Hunter: https://drughunters.com/3GDlp0s

07/10/2025

How to Use Drug Hunter to Improve Design Ideas
Tuesday, July 22nd, 2025
8 AM PT | 11 AM ET | 5 PM CET

One of the most common questions during the design process for new drug molecules is whether a particular structural motif appears in FDA-approved drugs or recent clinical candidates. In this webinar, we’ll show you how to answer that question in seconds using Drug Hunter's Structure Search. You’ll also discover how to refine your design ideas and gain inspiration from emerging structural trends—like bridged heterocycles—that are increasingly found in both clinical candidates and approved drugs.

Join us live and ask any design question you've been wrestling with!

Register here: https://drughunters.com/4kyd0cm

07/10/2025

BBO-10203, A Potential First-in-Class PI3Kα:RAS Protein-Protein Interaction Inhibitor Advances to Phase I Trials | https://drughunters.com/3U4LqZu

BBO-10203 is a potential first-in-class covalent inhibitor of the PI3Kα:RAS interaction, a critical oncogenic signaling pathway. BBO-10203 covalently binds to the RBD of PI3Kα at Cys242, effectively blocking its interaction with all RAS isoforms (K-, H-, and N-RAS), regardless of their mutation status. It’s currently in the Ph. 1 BREAKER-101 trial for advanced solid tumors

Learn more about BBO-10203, including its discovery, binding mode, how it mitigates adverse effects like hyperglycemia (a common challenge with PI3Kα-targeting agents), its preclinical profile, and much more in our full Drug Hunter case study!

Read more: https://drughunters.com/3U4LqZu

07/09/2025

JNJ-6640 Reveals Purine Deprivation Strategy Against Drug-Resistant TB | https://drughunters.com/3TwdLYr

JNJ-6640, recently reported by a consortium led by Janssen in collaboration with the University of Cape Town and the London School of Hygiene and Tropical Medicine, is a novel inhibitor of Mycobacterium tuberculosis PurF—an enzyme essential for purine biosynthesis.

Discovered through phenotypic screening and resistance mapping, JNJ-6640 selectively blocks bacterial PurF without targeting the human homolog, opening a new MoA that could overcome current drug resistance challenges. While not a clinical candidate due to metabolic instability, it provides a powerful foundation for future TB therapies.

Read it on Drug Hunter:
https://drughunters.com/3TwdLYr

07/08/2025

IRF5 Target Review: Highlighting Two Divergent Approaches to an "Undruggable" Transcription Factor | https://drughunters.com/4nBs7EI

Successful drugging of transcription factors remains a significant challenge within drug discovery. These proteins are notorious for lacking “classically” druggable pockets, and their roles are often key to fundamental cell processes, injudicious inhibition of which can lead to undesirable toxicology.

The transcription factor IRF5 has been implicated as a key player in a variety of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis, leading courageous drug hunters to pursue it as a target, despite the aforementioned challenges.

In this review we highlight the orthogonal approaches of two companies, HotSpot Therapeutics and Kymera Therapeutics, who have taken up the challenge of downregulating IRF5 activity, through allosteric modulation and protein degradation respectively.

Read it on Drug Hunter | https://drughunters.com/4nBs7EI

Targeting transcription factors for therapeutic intervention is a challenge in small molecule drug discovery. However excitement around IRF5, a key immune system regulator that is implicated in lupus...