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ORIC® Pharmaceuticals Presents Enozertinib Data in NSCLC Patients with HER2 Exon 20 Mutations at the ESMO Asia Congress 2025

On December 5, 2025 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported data from a Phase 1b trial of enozertinib (ORIC-114) at the ESMO (Free ESMO Whitepaper) Asia Congress 2025. Data in previously treated NSCLC patients with HER2 exon 20 mutations were presented at a poster session, and the poster can be found in the publication section of ORIC’s website here.

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Enozertinib Phase 1b Trial Design
Enozertinib is being evaluated in a Phase 1b trial in patients with locally advanced or metastatic NSCLC with HER2 exon 20 mutations. Notably, enrollment allows patients with active untreated brain metastases. Prior therapies include chemotherapy and HER2 targeted therapies. The primary endpoint of the trial is to determine the recommended Phase 2 dose (RP2D), and secondary endpoints include investigator-assessed objective response rate (ORR), disease control rate (DCR), and safety.

Previously Treated NSCLC Patients with HER2 Exon 20 Mutations
As of the August 29, 2025 cutoff date, 49 patients were dosed — 26 patients received 80 mg QD oral enozertinib and 23 patients received 120 mg QD. Patients were treated with up to 4 prior therapies, with 80% of patients having received prior chemotherapy and 35% having received a prior HER2 targeted therapy. Brain metastases were present in 47% of patients at baseline, including those with active brain metastases.

Preliminary Safety Analysis
Enozertinib was well tolerated with mostly Grade 1 or 2 treatment-related adverse events (TRAEs), and no significant off-target toxicities. Most frequent TRAEs included paronychia, diarrhea, and dermatitis acneiform. Only 2 patients discontinued treatment due to TRAEs. Higher rates of dose reductions occurred in the 120 mg cohort compared to the 80 mg cohort.

Preliminary Activity Analysis
Tumor responses were observed in both the 80 mg and 120 mg cohorts, including in patients with baseline brain metastases. Patients in the 80 mg cohort experienced deeper tumor regressions potentially due to the lower rate of dose reductions.

35% ORR (26% confirmed ORR) and 100% DCR in the 80 mg cohort
As of the data cutoff (at a median follow-up of 50 weeks), 32% of patients remained on treatment in both the 80 mg and 120 mg cohorts
Next Steps
Based on data generated in patients with EGFR exon 20 and EGFR atypical mutations, 80 mg QD oral enozertinib has been selected as the dose for potential Phase 3 development. Enrollment and follow-up continues in 1L NSCLC patients with EGFR exon 20 and EGFR P-loop and alpha C-helix compressing (PACC) mutations, with the next update expected in mid-2026, ahead of initiation of potential Phase 3 trial(s). Enrollment in HER2 exon 20 has been completed with no further development planned in this patient population.

Conference Call and Webcast Details
In conjunction with the ESMO (Free ESMO Whitepaper) Asia Congress, ORIC will host a conference call and webcast on Saturday, December 6, 2025, at 8:00 pm ET. To join the conference call via phone and participate in the live Q&A session, please pre-register online here to receive a telephone number and unique passcode required to enter the call. A live webcast and audio archive of the conference call will be available through the investor section of ORIC’s website at www.oricpharma.com. The webcast will be available for replay for 90 days following the presentation.

(Press release, ORIC Pharmaceuticals, DEC 5, 2025, View Source [SID1234661169])

Immatics Announces $125 Million Underwritten Offering

On December 5, 2025 Immatics N.V. (NASDAQ: IMTX, "Immatics" or the "Company"), a clinical-stage biopharmaceutical company and the global leader in precision targeting of PRAME, reported that it has agreed to sell 12,500,000 ordinary shares at $10.00 per share in an underwritten offering. The gross proceeds from the offering, before deducting the underwriting discount and offering expenses, are expected to be $125 million. The offering is expected to close on December 8, 2025, subject to customary closing conditions.

Jefferies, Leerink Partners and Cantor are acting as joint book-running managers for the offering.

A registration statement relating to the securities has been filed with the U.S. Securities and Exchange Commission (the "SEC") and was declared effective on April 3, 2025. The offering is being made only by means of a prospectus supplement and accompanying prospectus. When available, copies of the final prospectus supplement and the accompanying prospectus relating to the offering may be obtained free of charge from

Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, NY 10022, telephone: (877) 821-7388, email: [email protected];
Leerink Partners LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, telephone: (800) 808-7525, ext. 6105, email: [email protected];
Cantor Fitzgerald & Co., Attention: Capital Markets, 110 East 59th Street, 6th Floor, New York, NY 10022, e-mail: [email protected].
This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. Any offers, solicitations or offers to buy, or any sales of securities will be made in accordance with the registration requirements of the Securities Act of 1933, as amended.

(Press release, Immatics, DEC 5, 2025, View Source [SID1234661168])

Estrella Advances STARLIGHT-1 Trial into Phase II Following Positive DSMB Recommendation

On December 4, 2025 Estrella Immunopharma, Inc. (NASDAQ: ESLA) ("Estrella" or the "Company"), a clinical stage biopharmaceutical company developing CD19 and CD22-targeted ARTEMIS T-cell therapies to treat cancer and autoimmune diseases, reported that an independent Data Safety Monitoring Board (DSMB) has completed its review of safety data from the Phase I dose escalation portion of the STARLIGHT-1 trial. Based on the favorable safety profile observed, the DSMB recommended advancing the trial to Phase II, or the expansion phase, at the Recommended Phase II Dose (RP2D). The expansion phase will further evaluate the safety and preliminary efficacy of EB103, the Company’s CD19-redirected ARTEMIS T-cell therapy, in patients with relapsed/refractory (R/R) B-cell non-Hodgkin’s lymphoma (NHL).

In the Phase I dose escalation phase, no treatment-related serious adverse events (SAEs) were reported (n=9). Notably, the majority of patients treated are considered high-risk, including one with Central Nervous System (CNS) lymphoma. The high-dose cohort achieved a 100% complete response (CR) rate at Month 1 in all evaluable patients.

"The advancement of EB103 into the expansion phase of STARLIGHT-1 is a pivotal milestone for Estrella," said Cheng Liu, PhD, Chief Executive Officer of Estrella. "The excellent safety profile and a 100% complete response rate observed in the high-dose cohort in Phase I demonstrated EB103’s potential to overcome the toxicity barriers that have historically restricted CD19 CAR-T use. We believe EB103 may significantly expand the commercial reach of cell therapy and deliver a best-in-class solution to a broader NHL population, including high-risk subgroups previously ineligible for commercial CAR-T."

The expansion phase is designed as a multi-center, open-label study intended to further evaluate the safety and efficacy of EB103 at the RP2D in subjects (≥ 18 years of age) who have R/R B-cell NHL. Data from this expansion cohort will be used to determine the pivotal trial strategy for EB103. Current active sites include UC Davis Comprehensive Cancer Center and Baylor Scott & White Research Institute. Further details of the trial can be found at www.clinicaltrials.gov under NCT identifier: NCT06343311.

About EB103

EB103, a T-cell therapy, also referred to as Estrella’s "CD19-Redirected ARTEMIS T-Cell Therapy," utilizes ARTEMIS technology licensed from Eureka Therapeutics, Inc. ("Eureka"), Estrella’s parent company. Unlike a traditional CAR-T cell, the unique design of an ARTEMIS T-Cell, like EB103 T-cell, allows it to be activated and regulated upon engagement with cancer targets that use a cellular mechanism more closely resembling the one from an endogenous T-cell receptor. Once infused, EB103 T cells bind to and destroy CD19-positive cancer cells.

(Press release, Estrella Biopharma, DEC 4, 2025, View Source [SID1234661152])

Mission Bio’s Tapestri Single Cell Multi-Omics Platform for Exploratory Biomarker Analysis Supports Myeloproliferative Neoplasms (MPNs) Data Presentation at ASH 2025

On December 4, 2025 Mission Bio, Inc., a leader in single-cell multi-omic solutions for precision medicine, reported that its Tapestri Platform and custom assay development supported initial exploratory biomarker analysis data presented by Incyte at the ASH (Free ASH Whitepaper) 2025 conference in Orlando, Florida, in December. The data demonstrate Tapestri Platform’s ability to accelerate the understanding of Myeloproliferative Neoplasms (MPNs) disease biology at the single-cell level.

Myeloproliferative neoplasms (MPNs) are a type of blood cancer caused by genetic mutations in blood-forming stem cells. These mutations—found in the JAK2, TPO-R, or CALR genes—lead to uncontrolled growth of certain blood cells. INCA033989, an investigational monoclonal antibody, targets mutant calreticulin (CALR), a key driver in MPN pathogenesis.

The data presented at ASH (Free ASH Whitepaper) 2025 illustrate how the Tapestri’s single-cell data was leveraged to understand disease persistence and clonal expansion in MPNs. Subsequently, Tapestri’s single-cell DNA and protein profiling was applied to gain deeper insights into clonal evolution, disease progression, and treatment response in patients with MPNs.

The Tapestri Platform enables high-resolution detection of co-occurring mutations and cell surface protein expression, providing a more comprehensive picture of tumor heterogeneity and immune interactions in MPNs. By incorporating Mission Bio’s single-cell technology, Incyte was able to better characterize clonal diversity, track resistance mechanisms, and refine patient stratification strategies to help advance the development of precision therapies for MPNs.

"Our collaboration with Incyte highlights the role of single-cell multi-omics as an advanced clinical biomarker tool and the potential power of single-cell analysis in supporting targeted therapy development in the clinic," said Brian Kim, CEO at Mission Bio. "By unraveling the complexity of MPNs at the single-cell level, we can enhance complex biomarker analysis for targeted therapies in this space."

To learn more about Mission Bio, the Tapestri Platform, and Pharma Assay Development (PAD) services, please visit www.missionbio.com.

(Press release, Mission Bio, DEC 4, 2025, View Source [SID1234661151])

Orano Med Enters Next Phase of Collaboration with Roche

On December 4, 2025 Orano Med, a subsidiary of the Orano group specializing in nuclear medicine, reported that its long-standing collaboration with the multinational pharmaceutical company Roche (SIX: RO, ROG; OTCQX: RHHBY) is entering the next phase. Over the past years, the companies have conducted extensive preclinical research to develop a potential novel cancer treatment approach called "two-step pretargeted radioimmunotherapy" (or PRIT). This innovative technology, which pretargets the tumor with an antibody that is subsequently able to capture chelated lead-212 (212Pb) to target tumor cells, is now ready to advance into clinical development in humans. Orano Med will be responsible for the manufacturing of 212Pb, utilizing its industrial manufacturing platform in France and the US.

Nicolas Maes, Chief Executive Officer of the Orano group, commented: "We are very pleased about the progress made in collaboration with Roche for the development of a potential new treatment approach for cancer patients. After the licensing agreement signed with Sanofi last year for our most advanced clinical program, AlphaMedix, the achievement with this potential new drug candidate marks an important milestone that we accomplished jointly with another major player in the pharmaceutical industry. It illustrates our capacity to execute our long-term strategy, aimed at developing a solid pipeline of 212Pb-targeted alpha therapies to treat multiple oncology indications. In addition, thanks to the Orano Group’s expertise in the nuclear industry and its access to thorium-232, a scarce raw material required for producing 212Pb, Orano Med is also responsible for the entire production and distribution chain for these isotopes."

Julien Torgue, Chief Scientific Officer of Orano Med, commented: "The application of two-step pretargeted radioimmunotherapy represents a potentially game-changing advancement in radioligand therapies and cancer treatment more broadly. Instead of delivering radiation and targeting vector together, the novel technique separates the process into two precise steps: first, allowing time for antibodies to accumulate on the tumor, and then capturing the alpha particle emitting radioactive isotope lead-212, which allows for the precise targeting of cancer cells while sparing healthy tissue. In preclinical studies, we could already demonstrate both strong efficacy and, importantly, a reduction in off-target uptake in healthy tissues. If these results translate to the clinic, this could bring us a major step closer to a more effective and for patients also safer form of radioligand therapy. We are looking forward to further continue the development of this innovative approach with Roche."

Under the terms of the agreement, Orano Med and Roche have committed to develop this new therapeutic solution targeting a specific antigen known as carcinoembryonic (CEA), a cell surface glycoprotein overexpressed in several cancers. This antigen serves as a marker for various types of cancer, such as colorectal, pancreatic, and gastric cancers, as well as certain lung cancers. These are cancers for which the current therapeutic options are often limited or insufficient to meet patients’ needs. CEA shows restricted expression in normal tissues, making it a very suitable target for antibody-based therapies and radioimmunotherapy.

The Roche sponsored phase 1 clinical trial is expected to start in the first half of 2026, initiating the development of a broader platform dedicated to alpha radioimmunotherapies, underscoring Orano Med’s global leading position in the field of targeted alpha therapies.

About 212Pb two-step PRIT
Compared with conventional radioligand therapies (RLT), where the isotope and targeting moiety are co-delivered, pretargeted radioimmunotherapy (PRIT) uses a sequential approach. A tumor-targeting bispecific antibody (bsAb) is first administered, followed by a radioligand carrying the radioactive payload. The delay gives the bsAb the necessary time to accumulate on the tumor cells while unbound radioligand is rapidly cleared. It thus enables highly specific antibody targeting while remaining compatible with the relatively short half-life of 212Pb (10.6 hours). By introducing the cytotoxic radioligand only after the bsAb has largely cleared from circulation, radiation is concentrated in the tumor. This sequential approach is designed to minimize systemic radiation exposure, achieve high tumor-to-nontumor ratios, and thus improve safety and tolerability compared to other RLTs.

One of the main challenges of the PRIT approach has been to ensure fast excretion of the radioactive payload while maintaining high affinity for the slower-clearing pretargeting molecule. An intermediate step to clear or neutralize circulating pretargeting antibodies has often been employed to prevent off-tumor capture of the radioligand, but this adds complexity and safety risks, posing challenges to the clinical implementation of PRIT.

The new approach developed by Roche and Orano Med represents a novel two-step PRIT regimen for CEA-positive tumors that eliminates the need for an intermediate clearance step. This strategy combines a complementary bispecific antibody pair with the chelated ²¹²Pb, demonstrating both high efficacy and improved tolerability in preclinical studies compared with three-step PRIT.

Preclinical studies have confirmed proof of mechanism and therapeutic efficacy of the two-step PRIT, showing a favorable biodistribution with substantial uptake in CEA-positive tumors and rapid clearance of unbound 212Pb-DOTAM, with limited accumulation in kidneys and other organs. This confirms the excellent 212Pb tumor specificity and its high potential to significantly delay tumor growth.

(Press release, Orano Med, DEC 4, 2025, View Source [SID1234661150])