On May 26, 2022 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing first-in-class allogeneic gamma delta chimeric antigen receptor (CAR) T cell therapies for cancer, reported that an abstract detailing updated safety and efficacy data from the Company’s Phase 1 study of ADI-001 for the potential treatment of relapsed or refractory B-cell Non-Hodgkin’s Lymphoma (NHL) was made available as part of the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, to be held June 3-7, 2022 (Press release, Adicet Bio, MAY 26, 2022, View Source [SID1234615126]). The abstract provides a summary of clinical data as of a February 14, 2022, data-cut date.

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"We are very pleased to see the continued positive data resulting from our ongoing Phase 1 clinical trial evaluating ADI-001 in relapsed/refractory NHL. We believe that our allogeneic gamma delta CAR T cell therapy approach may improve complete response rate and durability by the complementary innate, adaptive and CAR-mediated anti-tumor response," said Chen Schor, President and Chief Executive Officer of Adicet. "We look forward to presenting updated data on safety, efficacy, pharmacokinetics and longer follow up, including available data from patients enrolled in dose level 3, at the upcoming 2022 ASCO (Free ASCO Whitepaper) Annual Meeting with a coinciding press release as well as a company webcast later that afternoon."

Data highlights as of the February 14, 2022 data-cut date included in the ASCO (Free ASCO Whitepaper) abstract were as follows:

Six evaluable patients were enrolled in dose level 1 (DL1; 30 million CAR+ cells) and dose level 2 (DL2; 100 million CAR+ cells), 33% (2/6) were female and the median age was 62 years (range 45-75). There were five patients with large B-cell lymphoma and one with mantle cell lymphoma. Indolent lymphomas, such as follicular lymphoma, are currently not enrolled in the study.
Overall, the patients were heavily pretreated with a median number of prior therapies of 3.5 (range 2-5) and had a poor prognostic outlook as indicated by the median International Prognostic Index (IPI) score of 3.5 (range 2-4). One patient previously progressed following two prior treatments with autologous anti-CD19 CAR T cell therapy (lisocabtagene maraleucel) prior to receiving ADI-001.
At Day 28, the overall response rate (ORR) and the complete response (CR) rate based upon independent central reading by PET/CT were 67% (4/6 patients).
As of the February 14, 2022 data-cut date, of the four patients who achieved CR after treatment with ADI-001:
Two patients remained in CR with ≥ three months post-treatment follow-up, including a triple-hit large B-cell lymphoma patient who had previously progressed following two administrations of autologous anti-CD19 CAR-T and a total of five lines of prior therapy.
As previously disclosed, one patient, a 66-year-old female who had responded to ADI-001, developed COVID-19 related pneumonia approximately two and a half months after ADI-001 administration and later died of complications from it, unrelated to ADI-001. This patient was previously reported as a partial response (PR) by local radiological assessment and has been assessed as a CR by independent central reading.
One patient with a CR had not reached the three-month assessment date as of the data-cut date for the ASCO (Free ASCO Whitepaper) abstract submission.
Safety data from the trial at the February 14, 2022 data-cut date were consistent with the previously reported well tolerated profile, with no occurrence of Grade ≥ 3 Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) or Graft vs Host Disease. No dose-limiting toxicities were documented.
All response data have been determined per protocol by independent central reading of PET/CT per Lugano (2014) criteria.
The full abstract is available online on the ASCO (Free ASCO Whitepaper) website.

Updated data from a May 31, 2022 data-cut date will be presented during an oral presentation by Sattva Neelapu, M.D. Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, at the ASCO (Free ASCO Whitepaper) Annual Meeting on June 6, 2022. Adicet will summarize the data from the May 31, 2022 data-cut date in a press release and provide additional information in a company webcast on June 6, 2022.

Details of the oral presentation are as follows:

Abstract Number: 7509
Abstract Title: A Phase 1 Study of ADI-001: Anti-CD20 CAR-engineered Allogeneic Gamma Delta (γδ) T cells in Adults with B-cell malignancies
Presenting Author: Sattva Neelapu, M.D., The University of Texas MD Anderson Cancer Center
Session Type/Title: Clinical Science Symposium/ Beating Bad Blood: The Power of Immunotherapy in Hematologic Malignancies
Date: Monday, June 6, 2022
Time: 8:00 AM-9:30 AM CDT

Adicet Investor Webcast/ Conference Call Information

The Company will host a conference call and webcast on June 6, 2022, at 4:30 p.m. ET to discuss the results. The live webcast of the presentation can be accessed under "Presentations & Events" in the investors section of the Company’s website at www.adicetbio.com or by dialing (877) 800-3802 (domestic) or +1 (615) 622-8057 (international) and reference the conference ID 5466375. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

About ADI-001

ADI-001 is an investigational allogeneic gamma delta CAR T cell therapy being developed as a potential treatment for relapsed or refractory B-cell NHL. ADI-001 targets malignant B-cells via an anti-CD20 CAR and via the gamma delta innate and T cell endogenous cytotoxicity receptors. Gamma delta T cells engineered with an anti-CD20 CAR have demonstrated potent antitumor activity in preclinical models, leading to long-term control of tumor growth. In April 2022, ADI-001 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the potential treatment of relapsed or refractory B-cell NHL.

About the GLEAN Study

This Phase 1 study is an open-label, multi-center study of ADI-001 enrolling adults diagnosed with B-cell malignancies who have either relapsed, or are refractory to at least two prior regimens. The primary objectives of the study are to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ADI-001, and to determine optimal dosing as a monotherapy. The study is expected to enroll approximately 75 patients. For more information about the clinical study design, please visit www.clinicaltrials.gov (NCT04735471).

On May 26, 2022 Caris Life Sciences(Caris), the leading molecular science and technology company actively developing and delivering innovative solutions to revolutionize healthcare reported that the company and partners within its Precision Oncology Alliance (POA) will collectively present 45 studies across more than 20 various solid tumor types at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from June 3-7, 2022 (Booth #22081) (Press release, Caris Life Sciences, MAY 26, 2022, View Source [SID1234615142]).

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"The breadth of research being presented at ASCO (Free ASCO Whitepaper) illustrates the power of comprehensive molecular profiling and large-scale collaboration between more than 60 sites to address some of the biggest challenges in cancer care and precision oncology today," said Chadi Nabhan, M.D., MBA, FACP, Chairman of the Caris Precision Oncology Alliance. "The findings of these studies could help improve outcomes for patients with difficult-to-treat cancers and pioneer new approaches to care across diverse tumor types and patient populations."

"At Caris, our goal is to enable clinicians to make the best treatment choices, researchers to discover new targets, and the biopharmaceutical industry to develop the next breakthrough medicines," said David Spetzler, M.S., Ph.D., MBA, President and Chief Scientific Officer of Caris. "These presentations show how our scientists and partners in the POA are using Caris’ unique AI-driven platform – which combines data from DNA (Whole Exome), RNA (Whole Transcriptome), and protein profiling with real-world clinical evidence from over 378,000 lifetime cases – to unravel the complexities of cancer. Ultimately, these discoveries could advance personalized cancer care and improve outcomes for many patients."

The Caris Precision Oncology Alliance includes 65 cancer centers and academic institutions in the United States and beyond. These institutions have early access to the extensive database and artificial intelligence platform within Caris to establish evidence-based standards for cancer profiling and molecular testing in oncology. By leveraging the comprehensive genomic, transcriptomic and proteomic data available through Caris molecular profiling, Caris seeks to provide this network with the ability to prioritize therapeutic options and determine which clinical trial opportunities may benefit their patients. POA members are also able to integrate with a growing portfolio of biomarker directed trials sponsored by biopharma. Additionally, as a member of the POA, institutions have access to Caris CODEai, the most comprehensive data solution in the industry with cancer treatment information and real-world clinical outcomes evidence for over 275,000 patients covering over 1 million data points per patient.

Three oral discussions focus on difficult to treat tumors and aggressive tumor types with low survival rates:

Comprehensive Genomic and Transcriptomic Characterization of Small Bowel Adenocarcinoma (Poster Number: 6)
June 4, 2022, 1:15-2:45 PM CDT

Biological and prognostic relevance of epigenetic regulatory genes in high-grade gliomas (HGGs) (Poster Number: 3570)
June 5, 2022, 11:30 AM-1:00 PM CDT

Surfaceome profiling revealed unique therapeutic vulnerabilities in transcriptional subtypes of small cell lung cancer (SCLC) (Poster Number: 142)
June 6, 2022, 11:30 AM-1:00 PM CDT
Other notable studies among the 45 accepted abstracts focus on key topics in oncology such as the tumor microenvironment, mechanisms of therapeutic resistance and rare biomarkers:

The tumor microenvironment and immune infiltration landscape of KRAS mutant pancreatic ductal adenocarcinomas (PDAC) compared to colorectal adenocarcinomas (CRC) (Poster Number: 127)
June 4, 2022, 8:00-11:00 AM CDT

Claudin 18 (CLDN18) gene expression and related molecular profile in gastric cancer (GC) (Poster Number: 36)
June 4, 2022, 8:00-11:00 AM CDT

The differential response to immune checkpoint inhibitors in colorectal and endometrial cancer patients according to different mismatch repair alterations (Poster Number: 418)
June 4, 2022, 8:00-11:00 AM CDT

Characterization of TIM3 and its ligands in colorectal cancer (Poster Number: 341)
June 4, 2022, 8:00-11:00 AM CDT

Exploring the nuances between BRCA1 and 2: a multiomic analysis (Poster Number: 456)
June 4, 2022, 1:15-4:15 PM CDT

S1314 Correlative analysis of ATM, RB1, ERCC2 and FANCC mutations and pathologic complete response (pT0) at cystectomy after neoadjuvant chemotherapy (NAC) in patients with muscle invasive bladder cancer (MIBC): implications for bladder preservation (Poster Number: 72)
June 4, 2022, 1:15-4:15 PM CDT

Reversion mutations in BRCA1 or BRCA2 genes: Resistant mechanism(s) in patients treated with platinum-based agents or poly (ADP-ribose) polymerase (PARP) inhibitors (Poster Number: 124)
June 5, 2022, 8:00-11:00 AM CDT

Characterization of MET exon 14 skipping alterations (METex14) in non–small cell lung cancer (NSCLC) using whole transcriptome sequencing (WTS) (Poster Number: 108)
June 6, 2022, 8:00-11:00 AM CDT
Poster and abstract summaries highlighting this research will be available onsite at Caris’ booth 22081. The full abstracts will be available through the official ASCO (Free ASCO Whitepaper) website on May 26.

On May 26, 2022 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, reported the publication of data showing the potential best-in-class safety profile of its anti-CTLA-4 monoclonal antibody (mAb), ADG126. Interim results from the Phase 1 dose escalation portion of an ongoing Phase 1b/2 trial of ADG126 are published in an abstract on the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting website in conjunction with the 2022 Annual Meeting taking place in Chicago from June 3-7, 2022 (Press release, Adagene, MAY 26, 2022, View Source [SID1234615159]).

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Key data in the abstract, titled "Phase 1 study of ADG126, a novel masked anti-CTLA-4 SAFEbody, that combines tumor-localized activation with strong Treg depletion and soft ligand blocking in patients with advanced solid tumors," include the following:

In this dose escalation of 16 patients with advanced metastatic solid tumors, approximately one third received three or more lines of prior therapies, and approximately one third had progressed from immuno-oncology (IO) therapy. ADG126 was administered to this heavily pretreated patient population intravenously as monotherapy once every three weeks at doses up to 10 mg/kg.
No dose-limiting toxicities or treatment-related SAEs were observed and only Grade 1 treatment related adverse events (TRAEs) were reported with repeat dosing across all dose levels; fatigue (19%) and pruritis (13%) were most common.
Plasma pharmacokinetics (PK) were approximately linear and the activated ADG126 accumulated steadily during repeat dosing across different dose levels. As the first clinical data validating the SAFEbody precision masking technology, the approximately 1.7-fold increase in half-life of total ADG126 is reflective of prolonged exposures of activated ADG126 in the tumor microenvironment (TME).
In an early indication of antitumor activity, two heavily pretreated patients with cold tumors (one ovarian and one uveal melanoma) showed durable reductions in target lesions (over 20%) and increased CD8+ T cells post-dosing. After the seventh cycle of ADG126 treatment at 1 mg/kg the ovarian cancer patient also showed a 77% reduction in CA-125 levels, an established biomarker of clinical benefit for ovarian patients. This activity is likely due to the accumulation of activated ADG126 in the TME upon repeat dosing at 1 mg/kg. The uveal melanoma patient was resistant/refractory to prior IO-IO combination therapy, having progressed on the combination of nivolumab and ipilimumab.
At the data cut-off of February 15, 2022, stable disease was seen in 5/16 patients, including the ovarian cancer and uveal melanoma patients. Dose escalation in this trial continues at 20 mg/kg and dose expansion has started at 10 mg/kg.
Commenting on the findings, Dr. Gary Richardson, OAM, MBBS, FRACP, Group Director at Cabrini Health Research, Neil Beauglehall Endowed Chair, Medical Oncology Research, and Professor of Medicine at Monash University, Australia, said, "With the emerging clinical data evaluating this novel immunotherapy candidate ADG126, a masked anti-CTLA-4 SAFEbody, we have the opportunity to detangle safety from efficacy, and deeply understand the benefits of Treg depletion while we optimize anti-CTLA-4 therapy as a cornerstone of future therapy. Another exciting and surprising aspect of these interim findings is that we see early signals of efficacy in certain ‘cold’ tumors with SAFEbody ADG126, which further builds on prior clinical evidence with its parental antibody ADG116, targeting a unique epitope of CTLA-4 to enable not only a safer but potentially better therapy than the options we have available today."

ADG126 SAFEbody applies precision-masking technology to the parental anti-CTLA-4 antibody, ADG116, for conditional activation in the TME to expand the therapeutic index and further address safety concerns with existing CTLA-4 therapies. Binding to the same unique epitope as ADG116, the masked ADG126 is designed to provide enhanced safety and efficacy profiles due to the combination of the potent Treg depletion in the TME and soft ligand blocking.

"Following these monotherapy dose escalation results, we look forward to releasing further data in coming months to confirm if the strong safety profile of ADG126 is preserved in combination with anti-PD-1 therapy, consistent with our preclinical observations," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene.

On May 26, 2022 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported the publication of an abstract at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Onconova, MAY 26, 2022, View Source [SID1234615195]). Featured in the abstract are preclinical data from in vitro and cell-based assays that demonstrate how narazaciclib’s inhibitory profile differentiates it from the FDA-approved CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib.

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Key data and conclusions from the abstract include:

Narazaciclib, abemaciclib, palbociclib, and ribociclib each have strong affinity for CDK4/cyclin D1, with Kd values of 0.18 nM, 0.08 nM, 0.75 nM, and 1.3 nM, respectively.

Narazaciclib and abemaciclib have similar affinities against CDK family members, including nM activity against CDK2/cyclin A, which may play a role in resistance to palbociclib and ribociclib.

Narazaciclib’s inhibitory activity against GSK3β, a kinase whose inhibition putatively causes tolerability issues related to diarrhea, is ~29 times less than that of abemaciclib.

Cellular kinase assays showed narazaciclib’s highest inhibitory activity to be against CDK4/6, CSF1R, (supports pro-tumor immune suppression), and NUAK1/ARK 5 (associated with poor prognosis in multiple cancers and implicated in cancer cell migration, invasion, and metastasis).

Cellular Thermal Shift Assay (CETSA) and integrative Inferred Kinase Activity (INKA) analysis showed that narazaciclib is associated with and modulated unique signaling pathways resulting in specific deregulated phosphorylation patterns when compared to palbociclib treated cells.
Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova and co-author of the abstract, commented, "Though revolutionary and commercially successful, currently available CDK4/6 inhibitors are limited by tolerability and safety issues as well as the unfortunate reality of primary and acquired drug resistance. This creates a pressing unmet need for novel agents that may overcome these shortcomings and provide patients with durable clinical benefit. Narazaciclib’s decreased affinity for targets associated with poor tolerability, together with its increased inhibitory activity against kinases implicated in metastasis, cancer cell survival, immune suppression, and drug resistance, suggests it may address this need. We continue to explore this hypothesis in narazaciclib’s clinical program and remain on track to establish a recommended Phase 2 dose by the end of the year."

A copy of the abstract, titled, "Narazaciclib’s kinase inhibitory activity is differentiated from approved CDK4/6 inhibitors in preclinical models," is available on the ASCO (Free ASCO Whitepaper) Annual Meeting website.

On May 26, 2022 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported that Troy Wilson, Ph.D., J.D., President and Chief Executive Officer, is scheduled to participate in three upcoming investor conferences (Press release, Kura Oncology, MAY 26, 2022, View Source [SID1234615062]):

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A virtual fireside chat at Cowen’s 3rd Annual Oncology Innovation Summit at 3:30 p.m. ET / 12:30 p.m. PT on June 2, 2022;

A fireside chat at the Jefferies Healthcare Conference in New York at 10:30 a.m. ET / 7:30 a.m. PT on June 8, 2022; and

A fireside chat at the JMP Securities Life Sciences Conference in New York at 2:30 p.m. ET / 11:30 a.m. PT on June 16, 2022.
Audio webcasts will be available in the Investors section of Kura’s website at www.kuraoncology.com, with archived replays available following each event.