On January 16, 2024 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, reported data from its presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 Gastrointestinal (GI) Cancers Symposium, taking place January 18-20 in San Francisco (Press release, Adagene, JAN 16, 2024, View Source [SID1234639974]).

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"The expanded therapeutic index for the masked ADG126 allows us to dose with a higher and more frequent effective dose of anti-CTLA-4 therapy than today’s options," said Daneng Li, MD and Associate Professor Department of Medical Oncology & Therapeutics Research at the City of Hope Comprehensive Cancer Center. "These promising data support further evaluation of this potential best-in-class anti-CTLA-4 antibody, ADG126, in combination with pembrolizumab for MSS CRC patients, including battling new liver lesions in those patients initially without detectable liver metastasis. We also see a tremendous opportunity to help patients in other tumor types where there is a significant need for safe and potent anti-CTLA-4 therapy."

Key highlights from the poster (November 30, 2023 data cutoff) include:

Results from dose escalation and dose expansion cohorts of ADG126 in combination with Merck & Co., Inc., Rahway, NJ, USA’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) (200 mg/Q3W) demonstrated a best-in-class safety profile for ADG126 at doses from 6 mg/kg to 10 mg/kg in heavily pre-treated advanced/metastatic patients (N=46):
Limited dose-dependent toxicities were observed.
Grade 3 TRAEs occurred in 5/46 patients (10.8%), with no Grade 4 or 5 TRAEs and a discontinuation rate of 6.5% (3/46).
In dose escalation across tumor types, two partial confirmed responses (PRs) were observed among the three patients treated with ADG126 10 mg/kg Q3W, which triggered expansion cohorts at this dosing regimen. One of the patients had PD-1 refractory cervical cancer and the other had endometrial cancer. Both confirmed PRs are sustained after more than 55 weeks (over 14 cycles) of treatment.
In dose expansion of patients with MSS CRC, 12 evaluable patients without liver metastases were treated at the active, potent dose of 10 mg/kg Q3W:
Two confirmed PRs were observed in nine of these patients without peritoneal and liver metastases, resulting in an overall response rate of 22% in this subset.
An additional seven of these nine patients experienced stable disease (SD) for an overall disease control rate 100% (2 PRs and 7 SD).
Observation of these clinical activities triggered further expansion into Stage 2 of the Simon’s 2-stage design for this dose level, which is currently ongoing with data anticipated throughout 2024.
In a preliminary PFS analysis of those MSS CRC patients free of liver and peritoneal metastasis, a median PFS of seven months was observed in those treated with ADG126 10 mg/kg at two dosing frequencies pooled together [every three weeks (n=9) and every six weeks (n=6)]. The durable clinical activity of ADG126 in combination with pembrolizumab will continue to be evaluated as a larger cohort of subjects becomes evaluable at the 10 mg/kg Q3W dose level.
Commenting on the results, Heinz Josef-Lenz, MD, FACP, Associate Director for Clinical Research and Co-leader of the Translational Science Program at the USC Norris Comprehensive Cancer Center (NCCC) said, "I believe that CTLA-4 is an essential part of an effective immunotherapy for MSS CRC, yet physicians have been limited by the safety challenges from first generation options. The clinical profile of ADG126 in combination with pembrolizumab presents a great opportunity for MSS CRC patients that otherwise have limited immunotherapy options available."

ASCO-GI Poster Presentation Details

Title: Results of a phase 1b/2 study of ADG126 (a masked anti-CTLA-4 SAFEbody) in combo with pembrolizumab (Pembro) in patients (Pts) with metastatic microsatellite-stable (MSS) colorectal cancer (CRC)

Date: Saturday, January 20
Time: 6:30 a.m. – 7:55 a.m. Pacific Time
Onsite Location: Moscone West
Abstract Number: 127
Poster Board: H12
Consistent with the ASCO (Free ASCO Whitepaper)-GI embargo policy, the data are being released today in conjunction with the abstract publication.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

On January 16, 2024 Celyad Oncology (Euronext: CYAD) (the "Company"), reported a fourth quarter 2023 business update and an outlook for 2024 (Press release, Celyad, JAN 16, 2024, View Source [SID1234639286]).

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Michel Lussier, interim Chief Executive Officer of Celyad Oncology, commented: "2023 has been a very important year for Celyad Oncology, after the changes that occurred in 2022. Our research team has made a remarkable progress to broaden the range of cancer indications that could be targeted by chimeric antigen receptor (CAR) T-cells and to tackle the main limitations of current CAR T-cell therapies. We have shared new data at several scientific and business conferences along the year, and published in high impact peer-reviewed journals. We are eager to see the impact of our efforts to unleash the power of our IP estate and stay at the forefront of next-generation CAR T-cell development."

2023 corporate accomplishments

•
On August 24, 2023, the Company announced that it obtained commitments from Fortress, Tolefi and other longstanding existing shareholders to subscribe to a capital increase of up to €9.8 million in 2 tranches:

•
A first tranche of 2.0 million was disbursed in the context of authorized capital as of September 4, 2023; and

•
A second tranche subscribed by Fortress was approved by the extraordinary shareholders’ meeting of November 14, 2023. Following this private placement, the Company believes that its existing cash and cash equivalents should be sufficient, based on the current scope of activities, to fund operating expenses and capital expenditure requirements into the second quarter of 2025.

2023 operational highlights

•
Multiplex short hairpin ribonucleic acid (shRNA) non-gene edited technology – All along 2023, we have collected and presented data validating our shRNA multiplexing approach:

•
We developed a chimeric micro-RNA (miRNA) cluster to enable multiplexing of shRNAs, designed for easy, efficient, and tunable downregulation of up to four target genes simultaneously in CAR T-cells;

•
Results detailing the technical aspects of the development of this platform have been published in Molecular Therapy – Nucleic Acids (Mol Ther Nucleic Acids. 2023, 34:102038). This publication has raised much interest from the community and was subjected to an editorial comment in the same volume of the Journal (Mol Ther Nucleic Acids. 2023, 34:102077);

•
Additional data which demonstrate feasibility of this approach in the context of allogeneic cell therapies or with the aim to create therapies able to overcome the coinhibitory effects of exhaustion markers were presented at several scientific conferences. Posters are available on the company’s website, at View Source

•
Multispecific NKG2D-based CAR T-cell platform – In 2023, we have compiled and presented data validating our multispecific approach targeting NKG2D ligands (NKG2DL):

•
We have developed different CD19/NKG2DL, BCMA/NKG2DL and PSMA/NKG2DL multispecific CAR T-cells, utilizing both tandem constructs – that encompass the extracellular domain of the natural NKG2D receptor fused to a scFv targeting CD19, BCMA or PSMA, or dual constructs – that co-express the NKG2D-based CAR with an anti-CD19, anti-BCMA or anti-PSMA CAR, respectively;

•
Our data provides the proof-of-concept that NKG2DL are valuable targets in a multispecific CAR approach and demonstrate our CD19/NKG2DL multispecific CAR T-cells are highly effective to counteract relapses due to CD19 antigen loss in vivo. In vitro data generated with BCMA/NKG2DL and PSMA/NKG2DL multispecific CAR T-cells further validate this approach in other hematological and solid indications. Posters are available on the company’s website, at View Source.

Financial highlights

As of December 31, 2023, the Company had cash and cash equivalents of €3.0 million and short-term investments of €4.0 million. The Company projects that its existing cash, cash equivalents and short-term investments should be sufficient to fund operating expenses and capital expenditure requirements into the second quarter of 2025. Therefore, the Company continues to project that its existing cash and cash equivalents will be sufficient to fund its estimated operating and capital expenditures over at least the next 12 months from the date of this press release.

Outlook for 2024

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More data and evidence in the context of the multispecific CAR T-cell platform and shRNA multiplexing approach will be shared in the first half of 2024, with the aim to develop assets ready for a potential initiation of clinical trials either by the Company and/or through strategic partnerships afterwards.

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Celyad Oncology will attend the 7th CAR-TCR Europe summit in London, UK (February 27-29, 2024), the must-attend forum to brainstorm and stay at the forefront of cell therapy innovations.

Financial Calendar 2024

•  April 5th, 2024

•  Full Year 2023 Financial Results

•  May 6th, 2024

•  Annual shareholders meeting

•  August 6th, 2024

•  First Half 2024 Interim Results

The financial calendar is communicated on an indicative basis and may be subject to change.

On January 16, 2024 Arcus Biosciences, Inc. (NYSE:RCUS) reported promising overall survival data from ARC-8, a Phase 1b study that is being co-developed with Gilead Sciences. ARC-8 is the study of quemliclustat, an investigational small molecule CD73 inhibitor, plus chemotherapy with or without zimberelimab, an investigational anti-PD-1 antibody, in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC) (Press release, Arcus Biosciences, JAN 16, 2024, View Source [SID1234639284]). The results will be presented during the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI).

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"A quemliclustat-based regimen appears to meaningfully prolong survival compared to what we typically observe in patients with mPDAC who receive chemotherapy alone, the standard of care for more than 30 years," said Zev A. Wainberg, MD, MSc, Co-Director of the GI Oncology Program at University of California Los Angeles and a principal investigator of the ARC-8 trial. "CD73 is highly expressed on pancreatic cancer cells, and I am encouraged to see early evidence that inhibiting CD73 with a small molecule has the potential to improve outcomes for people with mPDAC, without an observed clinically meaningful increase in toxicity, when combined with standard of care chemotherapy relative to historical data for chemotherapy alone."

The results to be presented include data from all patients (n=122) with treatment-naïve (first-line) mPDAC who received 100mg of quemliclustat plus chemotherapy with or without zimberelimab in the dose-escalation, dose-expansion and randomization cohorts of ARC-8. The data cutoff was June 19, 2023. Median overall survival (mOS) data for both quemliclustat-based regimens were numerically greater than historical benchmark data for chemotherapy alone, which has shown a mOS of approximately nine months.

An analysis was performed by the Medidata AI team, part of Medidata, a Dassault Systèmes company, whereby they constructed a Synthetic Control Arm of patients who were treated with gemcitabine/nab-paclitaxel in Phase 2 and 3 clinical studies in the first-line metastatic pancreatic cancer setting, on a post-hoc basis. Patients from these studies were matched 1:1 to the pool of 122 patients treated with the 100 mg quemliclustat-based regimens in ARC-8, based on demographics and key baseline characteristics such as ECOG performance status, liver metastasis, and history of prior surgery. The matched SCA was constructed based on a pre-specified analysis plan before OS data were unblinded and analyzed by the Medidata AI team. The analysis showed that the patients in ARC-8 lived longer than patients from the matched control arm. Specifically, these results showed that patients in ARC-8 experienced a:

37% reduction in the risk of death, HR=0.63 (CI: 0.47 – 0.85, p=0.0030) and a
5.9-month increase in mOS (15.7 vs 9.8 months) relative to the matched control arm.
The efficacy data for the pooled dose-escalation, dose-expansion and randomized arms, as well as the data from the SCA, are summarized below:

A2: Q+G/nP*
(n=29)

A1: QZ+G/nP**
(n=61)

Pooled Q100
QZ+G/nP***
(n=93)

All Pooled Q100
Q±Z+G/nP
(n=122)****

Post-hoc
Synthetic
Control Arm
(n=122)*****

Median OS, months (95% CI)

19.4 (12.1, 23.0)

14.6 (10.6, 21.5)

13.9 (11.1, 18.7)

15.7 (12.4, 20.9)

9.8 (7.8, 11.4)

Hazard Ratio

(95% CI)

HR=0.63 (0.47 – 0.85)

p=0.0030)

12-month OS

72.3%

60.9%

59.6%

62.7%

41.1%

Median PFS, months (95% CI)

8.8 (6.4, 12.6)

4.9 (3.7, 6.0)

5.4 (4.9, 7.3)

6.3 (5.4, 7.7)

5.5 (4.4, 6.6)

Hazard Ratio

(95% CI)

HR=0.78 (0.58‑1.05)

p=0.1102

ORR, % (95% CI)

41 (24, 61)

34 (23, 48)

38 (28, 48)

39 (29.9, 47.8)

41 (32.2, 50.3)

Q, Quemliclustat; Z, Zimberelimab; G/nP, gemcitabine / nab‑paclitaxel; CI, confidence interval
*Cohort A2 – patients randomized to Q+G/nP in the dose-expansion phase.
**Cohort A1 – patients randomized to QZ+G/nP in the dose-expansion phase.
***Pooled Q100 QZ+G/nP – treatment-naïve patients receiving 100 mg of quemliclustat plus zimberelimab and G/nP across dose- escalation, expansion and randomization phases.
****All Pooled – treatment-naïve patients receiving 100 mg of quemliclustat with or without zimberelimab across dose- escalation, dose-expansion and randomization phases.
*****Synthetic Control Arm (Historical Control) – Historical clinical trial data from patients treated with G/nP, balanced to the baseline characteristics of ARC-8 participants. The Synthetic Control Arm data were compared to the All Pooled group.

No new safety signals were observed in the study. The most common adverse events (Grade 3 or higher) were neutropenia (37.9%, 34.4% and 38.7%) and anemia (27.6%, 26.2% and 23.7%), respectively, for cohorts A2, A1 and Pooled Q100 QZ+G/nP. Five deaths were reported, and none were considered by the study investigators to be related to quemliclustat or zimberelimab.

Quemliclustat and zimberelimab are investigational molecules. Arcus and Gilead have not received approval from any regulatory authority for any use globally, and their safety and efficacy for the treatment of pancreatic cancer have not been established.

About Quemliclustat

Quemliclustat is an investigational, potent and selective small molecule CD73 inhibitor. CD73 is the primary enzymatic producer of immunosuppressive adenosine in the tumor microenvironment, and high CD73 expression is associated with significantly poorer prognosis in several tumor types. Quemliclustat has been shown to block the production of adenosine. Once the immunosuppressive effects of adenosine are removed, activation of antitumor immune cells may be restored, resulting in cancer cell death.

Arcus and Gilead are currently evaluating quemliclustat in combination with other molecules within the collaboration portfolio with chemotherapy, including Phase 2 studies in lung and upper gastrointestinal cancers.

About the ARC-8 Trial

The ARC-8 trial is a Phase 1b, open-label, dose-escalation and dose-expansion platform study to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic and clinical activity of combinations of the small molecule CD73 inhibitor quemliclustat, anti-PD-1 antibody zimberelimab and chemotherapy (gemcitabine / nab‑paclitaxel, or G/nP) in participants with advanced pancreatic cancer.

After the dose-escalation phase, quemliclustat 100 mg was selected as the dose for expansion. Patients were treated with quemliclustat 100 mg every two weeks plus standard doses of chemotherapy and zimberelimab (240 mg IV every two weeks) in Cohort A (treatment-naïve mPDAC) of the dose-expansion phase and then randomized 2:1 to receive quemliclustat plus zimberelimab and chemotherapy (Cohort A1) or quemliclustat plus chemotherapy (Cohort A2). Pooled analyses were conducted to reflect: 1) all treatment-naïve patients who received quemliclustat 100 mg plus zimberelimab and chemotherapy from dose-escalation and dose-expansion phases and 2) all treatment-naïve patients receiving 100 mg of quemliclustat with or without zimberelimab across dose-expansion and escalation phases. Endpoints included safety, overall response rate, median overall survival and progression‑free survival. More information about ARC-8 is available at: View Source

Additionally, an analysis comparing the All Pooled cohort to a Synthetic Control Arm (SCA) was conducted to address the differences in patient characteristics in the study cohorts, particularly in relation to decreased presence of liver metastases at baseline in cohort A2. The SCA consisted of historical clinical trial data from patients treated with G/nP, with baseline characteristics matched to those of ARC-8 participants.

About Pancreatic Cancer

Pancreatic cancer occurs in the pancreas, an organ located behind the stomach that helps with digestion and controlling blood sugar. Pancreatic cancer is one of the most aggressive cancers, with a dismal prognosis. Approximately 50% of patients with PDAC are diagnosed in the metastatic setting, which is associated with a 5-year survival rate of only 3%. Over 80% of pancreatic cancers are diagnosed at a late stage. The majority (over 90%) of pancreatic cancers are adenocarcinomas, a type of cancer that forms in tissues that line certain internal organs and release fluids like those that help with digestion. There have been limited advancements for treating pancreatic cancer, and chemotherapy has been the standard of care for more than 30 years.

On January 16, 2024 InnoCare Pharma (HKEX: 09969; SSE: 688428), a commercial-stage biotech company, reported that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for the Company’s B-cell lymphoma-2 (BCL2) inhibitor, ICP-248 (Press release, InnoCare Pharma, JAN 16, 2024, View Source [SID1234639283]). This is InnoCare’s fifth innovative drug to enter the clinical stage in the U.S.

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This is a Phase I study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of ICP-248 in hematologic malignancy patients.

ICP-248 is a novel, orally bioavailable BCL2-selective inhibitor, which aims to treat hematologic malignancies as a monotherapy or in combination with other therapies. The Phase I dose escalation trial of ICP-248 is ongoing in China, and the preliminary results demonstrated good efficacy and safety profiles.

BCL2 is an important regulatory protein of the apoptosis pathway, and its abnormal expression is related to the development of various hematologic malignancies. ICP-248 exhibits its anti-tumor effects by selectively inhibiting BCL2 and restoring the mechanism of programmed cell death.

Dr. Jasmine Cui, the Co-founder, Chairwoman and CEO of InnoCare said, "ICP-248 would become an important asset for the Company’s globalization after orelabrutinib. The current study results will support ICP-248 to treat hematologic malignancies as a monotherapy or in combination with other therapies. Meanwhile, InnoCare is dedicated to building a leading franchise in hemato-oncology, and we have developed multiple drugs that cover a variety of important hemato-oncology targets such as BTK, CD19, CD20xCD3, BCL2 and E-3 ligase to address unmet medical needs."

On January 16, 2024 Accurus Biosciences Inc. ("Accurus") reported that it has entered into a worldwide licensing agreement for its CLDN18.2 monoclonal antibody with ImmPACT Bio USA, Inc. ("ImmPACT Bio"), a clinical-stage company focusing on the development of next generation chimeric antigen receptor (CAR) T-cell therapies (Press release, Accurus Biosciences, JAN 16, 2024, View Source [SID1234639282]).

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"We are excited to announce that ImmPACT Bio chose to utilize our potential best-in-class CLDN18.2 antibody to develop next generation CAR T therapies," said Dr. Richard Zhang, chief executive officer of Accurus. "We believe ImmPACT’s programs have the potential to deliver differentiated and powerful therapies to benefit cancer patients."

Under the terms of the agreement, Accurus Biosciences has granted exclusive worldwide rights to ImmPACT Bio to develop and commercialize next generation cell therapies using a designated antibody from Accurus’ CLDN18.2 antibody portfolio. Accurus retains the rights to develop and commercialize its CLDN18.2 antibody portfolio for all non-cell based therapeutic applications. The financial terms were not disclosed