On March 28, 2024 Jacobio Pharma (1167.HK), a clinical-stage oncology company drugging the undruggable targets, reported its 2023 annual results (Press release, Jacobio Pharmaceuticals, MAR 28, 2024, View Source [SID1234641587]). The revenue was RMB63.5 million, the R&D investment was RMB372 million, the cash and cash equivalent at the end of 2023 was RMB 1.2 billion. Jacobio Pharma also announced its recent business progress and expected milestones.

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Dr. Wang Yinxiang, Chairman and CEO of Jacobio Pharma, said: "In the past year, Jacobio continued to make progress in our projects. We received approval for registrational phase III clinical trial of the combination therapy between our SHP2 inhibitor JAB-3312 and KRAS G12C inhibitor glecirasib. Our JAB-3312 became the first SHP2 inhibitor to enter into registrational trial. This milestone is consistent with our mission of ‘drugging the undruggable’. Meanwhile, the patient enrollment for pivotal trial of our core product glecirasib has been completed, and the NDA application expected to be submitted in the first half of 2024. This marks that Jacobio will enter into the commercial stage."

Development of core clinical stage products

KRAS G12C inhibitor Glecirasib (JAB-21822)

Non-small cell lung cancer (NSCLC)

The patient enrollment for pivotal trial of glecirasib monotherapy in ≥2L NSCLC patients harboring KRAS G12C mutation was completed. The NDA application is expected to be submitted to CDE (Center for drug evaluation, NMPA) in Q2 2024 as planned.
1L NSCLC is in combination with SHP2 inhibitor JAB-3312. The phase III registrational trial was approved by CDE.
Pancreatic cancer (PDAC)

The pivotal trial of glecirasib monotherapy in ≥2L PDAC patients was activated in China.
The results were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) GI Annual Meeting. The cORR was 41.9% (13/31) and the DCR was 93.5% (29/31). The median progression-free survival (mPFS) was 5.6 months.
Colorectal cancer (CRC)

The clinical results of glecirasib monotherapy and glecirasib combined with cetuximab in advanced colorectal cancer were presented at the Second JCA- AACR (Free AACR Whitepaper) Precision Medicine International Conference.
Phase III pivotal trial design of glecirasib monotherapy or glecirasib in combination with cetuximab is expected to be approved by CDE in Q2 2024.
Multi-tumors basket

Multi-tumors basket includes biliary tract cancer, gastric cancer, small bowel cancer, appendices cancer, etc.
The results were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) GI Annual Meeting. The cORR was 57.9%（11/19), DCR was 84.2%（16/19), mPFS was 7.0 months.
A phase II single arm pivotal trial is under communication with CDE.
SHP2 inhibitor JAB-3312

The Phase III pivotal trial of JAB-3312 in combination with glecirasib to treat 1L NSCLC patients has been approved by CDE, and this study in China is expected to initiated in Q3 2024. JAB-3312 is the very first SHP2 inhibitor entering a phase III registrational trial worldwide.
The clinical data of glecirasib in combination with JAB-3312 was published at the 2023 European Society for Medical Oncology Congress (ESMO 2023). Glecirasib (800mg once daily) + JAB-3312 2mg (once daily for 1 week on, then 1 week off) dosage yielded ORR of 86.7% (13/15) and DCR of 100% (15/15).
Long term safety and efficacy data have submitted to the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
Development of other clinical products

P53 Y220C activator JAB-30355: The IND has been approved by U.S. FDA (Food and Drug Administration), and phase I clinical trial is expected to be initiated in the second half of 2024. Preclinical data will be presented at the AACR (Free AACR Whitepaper) Annual Meeting 2024.
BET inhibitor JAB-8263: A Phase II trial of JAB-8263 monotherapy or combination therapies is planned to be initiated in the second half of 2024. Clinical data will be published at the 2024 European Hematology Association (EHA) (Free EHA Whitepaper) Congress.
Aurora A inhibitor JAB-2485: RP2D is anticipated to be determined in Q2 2024. The preclinical study of JAB-2485 was presented at the 2023 AACR (Free AACR Whitepaper).
Anti-CD73 humanized monoclonal antibody JAB-BX102: RP2D is anticipated to be determined in Q2 2024. The preclinical study of JAB-2485 was presented at the 2023 AACR (Free AACR Whitepaper).
PARP7 inhibitor JAB-26766: Preclinical data will be presented at the AACR (Free AACR Whitepaper) Annual Meeting 2024.
We are optimizing the clinical development strategy for PARP7 inhibitor JAB-26766, GUE (glutamine-utilizing enzyme) inhibitor JAB-24114, and LIF mAb JAB-BX300 considering the current treatment landscape and our resources available.
Development of other pre-clinical products

KRASmulti inhibitor JAB-23E73: The IND application is expected to be submitted in Q2 2024.
Clinical candidate for HER2-STING iADC JAB-BX400 is expected to be nominated in the second half of 2024.
As of December 31, 2023, Jacobio owned 340 patents or patent applications that are filed globally, of which 82 patents have been issued or allowed in major markets globally. During the performance period, Jacobio raised HKD159 million through public placing, and obtained RMB150 million from Beijing E-town Capital. As of December 31, 2023, Jacobio has RMB 1.2 billion cash and cash equivalent, providing sufficient cash reserves for R&D investment in the next 30-36 months. Jacobio repurchased and canceled 1.807 million shares, continuing to increase shareholder value.

Conference Call Information

Jacobio Pharma will hold a live conference call at 10:30 AM March 29 2024 Beijing time. Participants please register in advance through View Source

On March 28, 2024 Mustang Bio, Inc. ("Mustang") (Nasdaq: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for difficult-to-treat cancers and rare genetic diseases, reported its expansion into autoimmune diseases with MB-106, a personalized CD20-targeted, 3rd-generation autologous CAR T-cell therapy (Press release, Mustang Bio, MAR 28, 2024, View Source [SID1234641586]). MB-106 is being developed in a collaboration between Mustang and Fred Hutchinson Cancer Center ("Fred Hutch"). Mustang and Fred Hutch are in preliminary discussions to explore a potential Phase 1 investigator-sponsored clinical trial to evaluate MB-106 for the treatment of autoimmune diseases.

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"Mustang is leveraging its expertise in developing cell therapies to explore a new frontier in patient care," said Manuel Litchman, M.D., President and Chief Executive Officer of Mustang. "MB-106’s observed safety profile, encouraging efficacy data, and our robust manufacturing capabilities have the potential to translate to improved outcomes for patients with autoimmune diseases. We believe an investigator-sponsored clinical trial is the fastest and most cost-effective way to embark on this program and aim to enroll the first patient in a Phase 1 trial in the fourth quarter of this year to demonstrate clinical proof-of-concept. We are in discussions with Fred Hutch to determine the autoimmune indication(s) we plan to pursue in the first trial and look forward to sharing more details in the near future."

This expansion is supported by promising scientific evidence. Several antibody therapies targeting CD20 on B-cells have successfully transitioned from cancer to autoimmune diseases, such as rituximab for both lymphoma and rheumatoid arthritis. Additionally, clinical studies with CAR-T therapies have already demonstrated early success in the treatment of autoimmune conditions, with published reports showing remission in patients with refractory systemic lupus erythematosus and other autoimmune diseases.

MB-106 is currently in a Mustang-sponsored multicenter Phase 1/2 clinical trial for relapsed or refractory B-cell non-Hodgkin lymphomas ("NHL") and chronic lymphocytic leukemia ("CLL"). Mustang expects to enroll the first patient in a registrational study evaluating MB-106 for Waldenstrom macroglobulinemia ("WM"), a rare type of B-Cell NHL, in the second half of this year.

Dr. Litchman continued, "Data from the MB-106 Phase 1/2 multicenter trial presented at the recent 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting demonstrate strong clinical activity and a favorable safety profile, establishing feasibility of outpatient administration and building a foundation for the treatment of autoimmune diseases, where tolerance for the more severe toxicities observed with approved CAR-Ts is lower. Mustang believes MB-106 has the potential to bring personalized CAR T-cell therapy to a broader patient population through the expansion of indications and accessibility."

Scientists at Fred Hutch played a role in developing these discoveries, and Fred Hutch and certain of its scientists may benefit financially from this work in the future.

On March 28, 2024 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing and commercializing viral immunotherapies to help patients fight cancer, reported the presentation of updated data from an ongoing phase 1b clinical trial of its herpes simplex virus-1 (HSV-1) replication-competent viral immunotherapy candidate, CAN-3110, in patients with rHGG that has recurred after standard of care (SoC) treatment (Press release, Candel Therapeutics, MAR 28, 2024, View Source [SID1234641585]). The data were presented today during the 5th Glioblastoma Drug Development Summit in Boston, Massachusetts.

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"We have recently reported encouraging clinical and biomarker activity data observed after a single dose of CAN-3110 in patients with rHGG. We observed a nearly doubling of the expected median overall survival in this therapy-resistant patient population," said Francesca Barone, MD, PhD, Chief Scientific Officer of Candel. "The data presented today further supports that repeated doses of CAN-3110 are feasible and generally well-tolerated in rHGG, potentially further improving the clinical activity of this investigational medicine. Safety and tolerability of both repeated injections and serial biopsies, performed prior to the administration of CAN-3110, will be monitored to gauge disease progression and tissue response to treatment. We look forward to sharing additional biomarker and clinical activity data in the second half of this year."

To date, over 50 patients have been treated with a single dose of CAN-3110 in the phase 1b clinical trial of CAN-3110 in recurrent high-grade glioma (rHGG). The investigators observed a nearly doubling of the expected median overall survival (mOS) after a single CAN-3110 injection, achieving a mOS of ~12 months, compared to historical reports of less than 6 to 9 months in this therapy-resistant condition. Positive HSV-1 serology was a predictor of response and was associated with improved survival (mOS in this population reached 14 months). Results from the ongoing phase 1b clinical trial were published in Nature in Q4 2023. CAN-3110 received U.S. Food and Drug Administration (FDA) Fast Track Designation for treatment of rHGG in Q1 2024, based on these data.

"Dosing patients with multiple injections represents the next step forward in the development of CAN-3110 for rHGG," said Paul Peter Tak, MD, PhD, FMedSci, President and CEO of Candel. "The observed data suggest that repeated injections of CAN-3110 are well tolerated, supporting the design of a future phase 2 clinical trial in this indication. We’re excited by our recent progress — as illustrated by the publication in Nature, CAN-3110’s recent FDA Fast Track designation, and the collaboration with Batavia Biosciences — to accelerate the development and production of CAN-3110, along with our update presented today. Together, we hope this will help to accelerate the development of a better treatment for patients with high unmet need."

About the phase 1 clinical trial of CAN-3110 in rHGG

The clinical trial comprises three arms. In arm A, 41 patients with recurrent HGG received a single intratumoral injection of CAN-3110 (dose ranging from 1×106 plaque forming units (pfu) to 1×1010 pfu), including nine patients with multifocal/multicentric, deep or bilateral tumors associated with poor survival. After observing this regimen was generally well tolerated without dose-limiting toxicity, patients in arm B (n=9) received a single dose of cyclophosphamide (24 mg/kg) two days before CAN-3110 injection at doses of 1 x 108 pfu (n=3) and 1 x 109 pfu (n=6). The rationale is based on findings in mouse models, where cyclophosphamide improved viral persistence in injected tumors. In arm C, two cohorts of 12 patients with rHGG will receive up to six injections of CAN-3110 over a four-month period.

About CAN-3110

CAN-3110 is a first-in-class, replication-competent herpes simplex virus-1 (HSV-1) oncolytic viral immunotherapy candidate designed with dual activity for oncolysis and immune activation in a single therapeutic. Its activity is designed to be conditional to the expression of Nestin in cancer cells. CAN-3110 is being evaluated in a phase 1 investigator-sponsored clinical trial in patients with rHGG. In October 2023, the Company announced that Nature published results from this ongoing clinical trial. CAN-3110 was well tolerated with no dose-limiting toxicity reported and CAN-3110 plus prodrug was associated with improved survival. Positive HSV-1 serology was a predictor of response and was associated with improved survival. Increased infiltrating immune cells in the tumor microenvironment and expansion of the T cell repertoire after treatment were also associated with improved survival. In the clinical trial, the investigators observed a nearly doubling of the expected median overall survival after a single CAN-3110 injection, compared to historical reports of less than 6 to 9 months in this therapy-resistant condition. By comparison, survival in the anti-HSV1 positive patients who received CAN-3110 was more than 14 months.

Candel expects to initiate Investigational New Drug-enabling work in a second indication characterized by Nestin expression.

On March 28, 2024 Gilead Sciences, Inc. (Nasdaq: GILD) and Xilio Therapeutics, Inc. (Nasdaq: XLO) reported an exclusive license agreement to develop and commercialize Xilio’s Phase 1 tumor-activated IL-12 program, XTX301 (Press release, Xilio Therapeutics, MAR 28, 2024, View Source [SID1234641580]).

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Xilio Therapeutics is a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies. The company is using its proprietary tumor-activation platform to build a pipeline of novel, tumor-activated molecules, including antibodies, cytokines, bispecifics, and cell engagers, which are designed to optimize the therapeutic index and localize anti-tumor activity within the tumor microenvironment. XTX301 is currently being evaluated in a Phase 1 dose escalation trial in patients with advanced solid tumors.

"Xilio’s novel tumor-activation platform naturally complements Gilead’s clinical development program in difficult-to-treat cancers and expands our focus in immuno-oncology," said Bill Grossman, MD, PhD, Senior Vice President, Oncology Clinical Development, Gilead Sciences. "We believe IL-12 has the potential to treat a broad range of tumor types and are excited to partner with Xilio to advance XTX301, a tumor-activated IL-12, as a monotherapy and a combination therapy across a variety of solid tumors."

"Gilead’s confidence in our tumor-activated technology, combined with their deep expertise in developing and commercializing novel immuno-oncology products, will enable us to accelerate and expand the development of XTX301, our tumor-activated IL-12," said René Russo, Pharm.D., President and Chief Executive Officer of Xilio. "We look forward to collaborating with Gilead as we seek to deliver on the potential for XTX301 to provide a meaningful benefit for a range of tumor types, including immunologically cold tumors, while overcoming the severe toxicities historically associated with IL-12."

Terms of the Agreement

Under the terms of the agreement, Xilio granted Gilead an exclusive global license to develop and commercialize XTX301, Xilio’s tumor-activated IL-12. Xilio will receive $43.5 million in upfront payments, including a cash payment of $30.0 million and an initial equity investment by Gilead of $13.5 million in Xilio common stock at a premium. Xilio will be eligible to receive up to $604.0 million in additional contingent payments, including additional equity investments by Gilead, a transition fee and specified development, regulatory and sales-based milestones. Xilio will also be eligible to receive tiered royalties ranging from high single digits to mid-teens on annual global net product sales.

Xilio will be responsible for conducting clinical development of XTX301 in the ongoing Phase 1 clinical trial through dose expansion. Following the delivery by Xilio of a specified clinical data package for XTX301, Gilead can elect to transition responsibilities for the development and commercialization of XTX301 to Gilead, subject to the terms of the agreement and payment by Gilead of a $75 million transition fee. Prior to the potential transition fee, Xilio is eligible to receive up to a total of $29.0 million in additional equity investments and a development milestone payment.

Gilead does not exclude acquired IPR&D expenses from its non-GAAP financial measures. This transaction is expected to reduce Gilead’s GAAP and non-GAAP 2024 EPS by approximately $0.03 – $0.04.

About XTX301 (IL-12) and the Phase 1 Clinical Trial

XTX301 is an investigational tumor-activated IL-12 designed to potently stimulate anti-tumor immunity and reprogram the tumor microenvironment (TME) of poorly immunogenic "cold" tumors towards an inflamed or "hot" state. Xilio is currently evaluating the safety and tolerability of XTX301 as a monotherapy in patients with advanced solid tumors in a first-in-human, multi-center, open-label Phase 1 clinical trial. Please refer to NCT05684965 on www.clinicaltrials.gov for additional details.

On March 28, 2024 Theratechnologies Inc. ("Theratechnologies" or the "Company") (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported two posters will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024, demonstrating the potential of its SORT1+ Technology platform – including novel camptothecin-peptide conjugates and its lead investigational peptide drug conjugate (PDC) candidate, sudocetaxel zendusortide (TH1902), as anticancer treatments (Press release, Theratechnologies, MAR 28, 2024, View Source [SID1234641579]). The AACR (Free AACR Whitepaper) meeting is taking place April 5-10 in San Diego, CA.

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These preclinical presentations reinforce existing data for sudocetaxel zendusortide to activate anti-PD-L1 immunotherapy tumor cell killing in SORT+1 cancers and provide the first evidence for novel camptothecin-peptide conjugates in the treatment of SORT+1 colorectal cancers.

"The studies we are presenting at the AACR (Free AACR Whitepaper) 2024 meeting highlight the significant advancements made on our SORT+1 Technology platform through careful assessment of investigational compounds, including sudocetaxel zendusortide, which is currently being evaluated in a Phase 1 trial in patients with advanced ovarian cancer," said Christian Marsolais, Ph.D., Senior Vice President and Chief Medical Officer of Theratechnologies. "These data showcase the potential of our PDC candidates with different payloads as potential future treatment options for a broad range of cancer types."

Theratechnologies will present the following data at AACR (Free AACR Whitepaper) 2024:

Monday April 8, 2024: 9:00am-12:30pm Pacific Time (PT)

Title: Pre-clinical evidence for new camptothecin-peptide conjugates in the treatment of sortilin-positive colorectal cancers

Presenting Author: Sanjoy Kumar Das, Ph.D., Theratechnologies
Session Category: Experimental and Molecular Therapeutics
Session Title: New Technologies
Location: Poster Section 28
Poster Board Number: 28
Abstract Presentation Number: 2071
Monday April 8, 2024: 1:30pm- 5:00pm Pacific Time (PT)

Title: Sudocetaxel Zendusortide (TH1902) triggers the cGAS/STING pathway and potentiates anti-PD-L1 immune-mediated tumor cell killing

Presenting Author: Michel Demeule, Ph.D., Theratechnologies
Session Category: Clinical Research Excluding Trials
Session Title: Combination Immunotherapies
Location: Poster Section 43
Poster Board Number: 3
Abstract Presentation Number: 3717

About Sudocetaxel Zendusortide (TH1902) and SORT1+ Technology

Sudocetaxel zendusortide is a first-of-its-kind sortilin receptor (SORT1)-targeting PDC, and the first compound to emerge from the Company’s broader licensed oncology platform. A new chemical entity, sudocetaxel zendusortide employs a cleavable linker to conjugate (attach) a proprietary peptide to docetaxel, a well-established cytotoxic chemotherapeutic agent used to treat many cancers. The FDA granted Fast Track designation to sudocetaxel zendusortide as a single agent for the treatment of all sortilin-positive recurrent advanced solid tumors that are refractory to standard therapy. Sudocetaxel zendusortide is currently being evaluated in a Phase 1 clinical trial.

Theratechnologies has established the SORT1+ TechnologyTM platform as an engine for the development of PDCs that target SORT1, which is expressed in multiple tumor types. SORT1 is a "scavenger" receptor that plays a significant role in protein internalization, sorting, and trafficking. Expression of SORT1 is associated with aggressive disease, poor prognosis, and decreased survival. It is estimated that SORT1 is expressed in 40% to 90% of endometrial, ovarian, colorectal, triple-negative breast (TNBC), and pancreatic cancers, making this receptor an attractive target for anticancer drug development.