On October 24, 2025 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported preclinical data for ARV-806, a PROTAC KRAS G12D degrader, at the 2025 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in Boston, Massachusetts. The ARV-806 data presented show a differentiated profile based on degradation potency, antiproliferative activity, and induction of cancer cell death. ARV-806 is designed to target both the ON and OFF forms of KRAS G12D, which is the most common mutation of the KRAS protein. ARV-806 has the potential to address high unmet need in solid tumors, such as pancreatic, colorectal and non-small cell lung cancer.

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"These data suggest the potential of targeted protein degradation to overcome historical limitations in addressing undruggable KRAS mutations," said Angela Cacace, Ph.D., Chief Scientific Officer of Arvinas. "ARV-806’s ability to eliminate both ON and OFF forms of KRAS G12D, combined with its potency and durability shown in preclinical models, supports our confidence in its clinical potential to deliver meaningful benefit for patients with KRAS G12D-mutated cancers."

Key highlights from the presentation include:

In vitro, ARV-806 degraded KRAS G12D with picomolar potency across pancreatic, colorectal, and lung cancer cell lines but did not induce degradation of wild-type and other mutant RAS isoforms.
ARV-806 is differentiated from other KRAS G12D targeting agents in development and has potential to be a best-in-class therapy for KRAS G12D mutated cancers due to:
Catalytic activity, which allows it to overcome upregulation, a common mechanism of resistance to inhibitor treatment
Compared with clinical-stage KRAS G12D ON and OFF inhibitors and another clinical-stage G12D degrader, ARV-806 demonstrated:
>25-fold greater potency in reducing cancer cell proliferation,
>40-fold higher potency in degrading KRAS G12D protein (versus the comparable clinical-stage G12D degrader), and
>10-fold lower concentrations required to induce pro-apoptotic BIM expression.
Following a single intravenous dose in a colorectal tumor xenograft model, ARV-806 degraded >90% of KRAS G12D for seven days, with parallel suppression of c-MYC (a key driver of cancer cell proliferation) and induction of BIM (Bcl-2-interacting mediator of cell death, a pro-apoptotic factor) for ≥5 days.
ARV-806 demonstrated robust efficacy responses at low doses in tumor models including: ≥30% tumor volume reductions in pancreatic and colorectal cell line-derived xenograft (CDX) models and a patient-derived xenograft (PDX) model of lung cancer.

These data demonstrate sustained pharmacodynamic activity consistent with long-lasting target degradation, which we believe supports intermittent clinical dosing. Arvinas is currently evaluating ARV-806 in a Phase 1 clinical trial in patients with KRAS G12D–mutated advanced solid tumors (NCT07023731).

Also shown in the poster, orally bioavailable pan-KRAS degraders have been identified that potently degrade multiple variants of KRAS and spare other RAS isoforms. A tool pan-KRAS PROTAC demonstrated robust single-agent activity and superior combination efficacy with immune checkpoint blockade compared with a pan-RAS ON inhibitor (7 complete responses compared with 2 complete responses).

About ARV-806
ARV‑806 is a novel, investigational PROTAC degrader designed to selectively target and degrade mutant Kirsten rat sarcoma (KRAS) G12D which is the most common mutation of the KRAS protein. Therefore, ARV-806 has the potential to address high unmet need in solid tumors, such as pancreatic, colorectal and lung cancer. ARV‑806 is currently being evaluated in a Phase 1 clinical trial in patients with advanced solid tumors harboring KRAS G12D mutations.

(Press release, Arvinas, OCT 24, 2025, View Source [SID1234656974])

On October 24, 2025 Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), an oncology company developing innovative, full-length multispecific antibodies and antibody drug conjugates (Biclonics, Triclonics and ADClonics), reported interim clinical data as of a July 29, 2025 data cutoff from the ongoing phase 2 trial of the bispecific antibody petosemtamab in combination with standard of care FOLFOX/FOLFIRI in 1L and 2L metastatic colorectal cancer (mCRC), and petosemtamab monotherapy in 3L+ mCRC. These data will be presented in a plenary session oral presentation by Dr. Moh’d Khushman M.D., Washington University School of Medicine, St. Louis, MO, at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) on Friday, October 24 at 10:20 a.m. ET.

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"Petosemtamab’s unique mechanism of action, including targeting both EGFR and LGR5, and potential to safely combine with FOLFOX/FOLFIRI, represents an important finding for patients with EGFR inhibitor-naïve metastatic colorectal cancer," said Fabian Zohren, M.D., Ph.D., Chief Medical Officer of Merus. "These data demonstrate petosemtamab’s clinical activity beyond head and neck squamous cell carcinoma. We are encouraged that petosemtamab has the potential to become a transformational treatment and new standard of care for patients across a range of solid tumors."

"Metastatic colorectal cancer remains a formidable challenge with limited effective therapies. The promising early results with petosemtamab offer hope for advancing care and bringing new treatment possibilities to patients facing this difficult disease," added Dr. Khushman.

Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics)

Presentation title: Petosemtamab (MCLA-158) monotherapy or with chemotherapy in metastatic colorectal cancer: Preliminary antitumor activity and safety data from a phase 2 trial
Observations in the presentation include:
As of a July 29, 2025 data cutoff date:

54 patients (pts) with left- and/or right-sided, KRAS, NRAS, and BRAF wildtype microsatellite stable mCRC received petosemtamab 1500 mg every two weeks, in combination with FOLFOX/FOLFIRI or as monotherapy
Pts treated in 1L or 2L had no prior anti-EGFR therapy
Pts treated in 2L received 1 prior chemotherapy regimen in the metastatic setting
Pts treated in 3L+ received at least 2 prior regimens in the metastatic setting, including a prior anti-EGFR therapy
Efficacy evaluable population consisted of patients with ≥1 dose of petosemtamab who had opportunity for ≥8 weeks follow up and ≥1 post baseline tumor assessment or discontinued petosemtamab early due to disease progression, symptomatic deterioration and/or death
1L petosemtamab with FOLFOX/FOLFIRI
14 pts were treated in 1L (10 FOLFOX and 4 FOLFIRI)
10 pts were efficacy evaluable, 8 left-sided; 10 (100%) remained on treatment
80% (8 of 10) response rate: 1 confirmed complete response, 7 partial responses (PRs) (4 unconfirmed of which 1 confirmed post data cutoff); 2 stable diseases (SDs)
88% (7 of 8) response rate in left-sided: 1 confirmed complete response, 6 PRs (3 unconfirmed, 1 unconfirmed response confirmed post data cutoff); 1 SD
One SD observed to be an unconfirmed PR post data cutoff leading to 100% (8/8) response rate left-sided and 90% (9/10) response rate overall in 1L
All unconfirmed PRs remained on treatment without disease progression
2L petosemtamab with FOLFOX/FOLFIRI
14 pts were treated in 2L (2 FOLFOX and 12 FOLFIRI)
13 were efficacy evaluable; 10 (77%) remained on treatment
62% response rate: 8 PRs (3 unconfirmed of which 1 confirmed post data cutoff); 4 SDs and 1 clinical deterioration prior to first scan
All unconfirmed PRs and SDs remained on treatment without disease progression
3L+ petosemtamab monotherapy:
26 pts were treated
20 were efficacy evaluable, 6 (30%) remained on treatment
10% confirmed response rate: 2 PRs; 9 SDs (5 remained on treatment)
Safety:
Petosemtamab safety profile in mCRC observed thus far, appears consistent with its established safety profile in recurrent/metastatic head and neck squamous cell carcinoma
No significant overlapping toxicities identified in combination with FOLFOX/FOLFIRI
No new safety signals identified
Infusion related reactions (IRRs) were managed with premedication and prolonged infusion on cycle 1 day 1; no discontinuations due to IRRs
Presentation:
Title: Petosemtamab (MCLA-158) monotherapy or with chemotherapy in metastatic colorectal cancer: Preliminary antitumor activity and safety data from a phase 2 trial
Session Title: Plenary Session 4: Clinical Trials Plenary Session
Date and Time: Friday, October 24, 10:20 a.m. ET
The same data will also be available in a poster:
Session Title: Poster Session B
Session Date and Time: Friday, October 24, 12:30-4:00 p.m. ET

As full presentations become available at the conference, they will contemporaneously be available on the Merus website.

(Press release, Merus, OCT 24, 2025, View Source [SID1234656991])

On October 23, 2025 Coherus Oncology, Inc. (NASDAQ: CHRS) reported that the company will be webcasting its presentations at the following upcoming conferences:

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UBS Global Healthcare Conference in Palm Beach Gardens, FL on Monday, November 10, 2025, at 1:15 p.m. Eastern Time / 10:15 a.m. Pacific Time
Jefferies Global Healthcare Conference in London, England on Tuesday, November 18, 2025, at 10:30 a.m. Greenwich Mean Time / 5:30 a.m. Eastern Time
Baird Biotech Discovery Series takes place virtually on Wednesday, December 17, 2025, at 1:30 p.m. Eastern Time / 10:30 a.m. Pacific Time
The presentations will be accessible via webcast links on the Investor Events section of the Coherus website: View Source Replays of the presentations will be available for 30 days.

If you would like to request a one-on-one meeting with company management during the conferences, please reach out to your respective bank representative.

(Press release, Coherus Oncology, OCT 23, 2025, View Source [SID1234656940])

On October 23, 2025 MIT reported the pills are by far the most convenient form of cancer treatment, but most oral cancer drugs quickly dissolve in the stomach, delivering a burst of chemicals into the bloodstream all at once (Press release, Enzian Pharmaceutics, OCT 23, 2025, View Source [SID1234656957]). That can cause side effects. It also may limit the drug’s effectiveness because its concentration in the blood may become too low after the initial burst.

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Now, the startup Enzian Pharmaceutics, founded by Aron Blaesi PhD ’14 and former principal research scientist Nannaji Saka ScD ’74, is developing an oral tablet that delivers drugs into the gastric fluid and the blood steadily over time. The company’s tablets use tiny 3D-printed fibers that turn into a gel-like substance when exposed to water. The tablets have been shown to stay in the stomach of animals for up to a day, slowly degrading while releasing the drug in controlled quantities.

The company is currently validating its tablets’ ability to stay in place in a small number of healthy human volunteers. In about a year, it plans to begin testing the technology’s ability to improve the effectiveness and safety of cancer drugs in patients.

"A lot of orally delivered cancer drugs could benefit from this," says Blaesi, who incorporated the company in 2016. "Right now, soon after someone has taken a cancer drug, its concentration in the blood can be up to 50 times greater than when they are supposed to take the next pill. During the peak, the drug goes into the heart, it goes into the liver, the brain, and it can cause a lot of problems, while at the end of the dosing interval the concentration in the blood may be too low. By taking out that peak and increasing the time the drug is released, we could improve the effectiveness of treatments and mitigate certain side effects."

In search of innovation
When Blaesi came to MIT, he knew he wanted his mechanical engineering PhD work to form the basis of a company. Early on, as part of the Novartis-MIT Center for Continuous Manufacturing, he worked on manufacturing pills with an injection molding machine that melted and solidified the material, in contrast to the traditional process of compacting powder. He noticed injection molding made the pills far less porous.

"If you put a typical pill into a fluid or into the stomach, the fluid percolates the pores and quickly dissolves it," Blaesi explains. "That’s not the case when you have an injection molded product. That’s when Dr. Saka, who I met almost daily to discuss my research with, and I started to realize that microstructure is very important."

The researchers began exploring how different tablet microstructures changed the rate at which drugs are released. For more precision, they moved from injection molding to 3D printing.

Using MIT machine shops, Blaesi built a 3D printer and produced tightly wound microstructures that could carry the drugs. He focused on fibrous structures with space between the fibers, because they would allow gastrointestinal fluid to percolate the pill and dissolve rapidly. He tested the structures in both his Cambridge, Massachusetts, apartment and at MIT’s shared facilities.

Blaesi then experimented with different carrier materials, finding that the higher the molecular weight, the longer it took the pill to dissolve because the material would absorb water and expand before degrading.

"Initially I thought, ‘Oh no, the drug isn’t being dissolved fast enough anymore,’" Blaesi recalls. "Then we thought, ‘Everything has its place.’ This could stay in the stomach for longer because of the expansion. Then it could release the drug over time. We realized this wouldn’t just improve manufacturing, it would improve the product."

In 2019, Blaesi and Saka published the first paper on their expandable fibrous tablets for prolonged drug delivery. It received a mixed reception.

"Some reviewers said, ‘Research on similar gastroretentive dosage forms has been done for 40 years and no one’s really succeeded,’" Blaesi recalls. "People said, ‘It will never work. Do experiments in animals and then we’ll talk.’"

Blaesi moved back to Switzerland during the Covid-19 pandemic and ran his animal experiments there.

"The reviewers were right: What we had didn’t work," Blaesi says. "But we adjusted the design and showed we could make the pill stay in the stomach for longer."

Inside Enzian’s final tablet design, tiny fibers are arranged in a grid. When water flows into the spaces between the fibers, they expand to form a strong gel-like substance that slowly erodes in the stomach, steadily releasing the drug. In animal studies, Enzian’s team showed its technology allowed tablets to remain in the stomach for 12 to 24 hours before being safely excreted.

The team soon found cancer drugs would be a good fit for their technology.

"A lot of cancer drugs are only soluble in acidic solutions, so they can only be absorbed while the drug is in the stomach," Blaesi explains. "But on an empty stomach, the drug may be in the stomach for just 30 or 40 minutes at present. For a full stomach, it’s a few hours. And because you have a short time to deliver the drug, you need to release a high dose immediately. That shoots up the blood concentration, and if you dose every 12 hours, the concentration is going down during the other 10 hours."

From the lab to patients
In upcoming human trials, Enzian plans to use its tablets to deliver a drug for prostate cancer that Blaesi says is currently dosed at several hundred milligrams a day. He hopes to get down to about a tenth of that with a better therapeutic effect.

Enzian also believes its technology could improve treatments for blood, skin, and breast cancers.

"This could really be used to improve treatment for a variety of cancers," Blaesi says. "We believe this is a more efficient and effective way to deliver drugs."

Maximizing effectiveness and minimizing side effects is also important in clinical trials, where a new drug’s superiority over existing treatments must be shown, and a single adverse event can end its development.

The upcoming move into patients is the culmination of more than a decade of work for Blaesi, who is confident Enzian can deliver on its promise of improving treatments.

"The opportunity is enormous," Blaesi says. "So many oral cancer drugs have this delivery problem. We still have to do the efficacy and safety studies on patients, but we expect this to be a game changer."

On October 23, 2025 Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) reported three abstracts from its clinical development programs will be presented at the upcoming North American Neuroendocrine Tumor Society Annual Meeting (NANETS 2025), taking place October 23-25, 2025, in Austin, Texas.

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"At the 2025 NANETS annual meeting, we are excited to showcase the continued progress of multiple development programs focused on the treatment of neuroendocrine tumors (NETs)," said Dana Pizzuti, M.D., Chief Medical and Development Officer at Crinetics. "For the first time, we will present progression-free survival data from our Phase 2 study of paltusotine for the treatment of carcinoid syndrome associated with NETs. Details of recently-initiated clinical trials for both paltusotine and our nonpeptide drug candidate (NDC) CRN09682 program will also be presented, demonstrating our deep commitment and continued momentum in the NETs space."

A preliminary analysis of Phase 2 data from the open-label trial of paltusotine in the treatment of patients with carcinoid syndrome due to NETs will be featured in a poster presentation, showing an overall investigator-assessed progression free survival rate of 74% following one year of treatment.

Paltusotine is approved as PALSONIFY in the U.S. as a once-daily oral for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. Paltusotine is currently being investigated for new indications, including for the treatment of carcinoid syndrome; it is not currently approved in the U.S. or any other countries for the treatment of carcinoid syndrome.

Two additional poster presentations will feature study details from the randomized, Phase 3 trial of paltusotine in carcinoid syndrome due to NETs and the first-in-human study of NDC candidate CRN09682 in patients with somatostatin receptor 2-expressing tumors.

Details on the abstracts to be presented at NANETS are shown below:

Title: Investigator-Assessed Disease Progression in a Phase 2 Study of Paltusotine in Patients with Neuroendocrine Tumors and Carcinoid Syndrome
Date/Time: October 23, 2025; 5:15 pm – 6:30 pm

Title: CAREFNDR: Phase 3, Randomized, Placebo-Controlled Study of Paltusotine in Adults With Carcinoid Syndrome Due to Well-Differentiated Neuroendocrine Tumors
Date/Time: October 23, 2025; 5:15 pm – 6:30 pm

Title: First-in-Human Study of a Novel Nonpeptide Drug Conjugate (CRN09682) in Patients With Somatostatin Receptor 2-Expressing Tumors
Date/Time: October 23, 2025; 5:15 pm – 6:30 pm

About Paltusotine  
Paltusotine, a selectively-targeted somatostatin receptor type 2 (SST2) nonpeptide, is in Phase 3 clinical development for carcinoid syndrome associated with neuroendocrine tumors (CAREFNDR). Results from a Phase 2 study in carcinoid syndrome demonstrated rapid and sustained reductions in flushing episodes and bowel movement frequency, which are the most common symptoms of carcinoid syndrome. PALSONIFY (paltusotine) is currently approved in the U.S. for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option.

ABOUT CRN09682
CRN09682 is an investigational, potentially first-in-class, non-radioactive, nonpeptide drug conjugate (NDC) linking a somatostatin receptor 2 (SST2) agonist with the cytotoxic drug monomethyl auristatin E (MMAE) via a spacer and a cleavable linker for the treatment of neuroendocrine tumors (NETs) and potentially for use in other solid tumors that express SST2. The SST2 ligand on the NDC molecule binds to SST2 on the tumor cell surface and is internalized in the cell whereby enzymes cleave the MMAE and release it within the cell. MMAE is known to cause microtubule disruption leading to cell arrest and death. The NDC approach is intended to enhance tumor penetration, selectively bind to specific GPCR expressing tumor cells, induce internalization, and intracellularly release a potent anti-tumor agent, while minimizing systemic exposure and associated toxicities. Additionally, NDCs are manufactured by traditional chemical synthesis methods, avoiding the limitations of fermentation, bioconjugation, and heterogeneous manufacturing methods required by most ADCs. NETs are generally incurable when metastatic, regardless of tumor grade. Overall survival rates vary significantly by stage, grade, age at diagnosis, primary site, and time period of diagnosis.

(Press release, Crinetics Pharmaceuticals, OCT 23, 2025, View Source [SID1234656941])