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Poseida Therapeutics Presents New Phase 1 Data at AACR 2024 Supporting Potential of P-BCMA-ALLO1 Allogeneic CAR-T Therapy to Benefit Broad Range of Patients with Multiple Myeloma

On April 8, 2024 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage cell and gene therapy company advancing a new class of treatments for patients with cancer and rare diseases, reported new data from a subset of patients in an ongoing Phase 1 study of its lead program, P-BCMA-ALLO1 (Press release, Poseida Therapeutics, APR 8, 2024, View Source [SID1234641877]). Results showed that three of the five (60%) patients with relapsed/refractory multiple myeloma who had progressed following BCMA-targeted therapy achieved clinical responses with P-BCMA-ALLO1. In addition, this investigational treatment was well-tolerated.

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P-BCMA-ALLO1 is a novel investigational B-cell maturation antigen (BCMA)-targeted allogeneic, T stem cell memory (TSCM)-rich chimeric antigen receptor T-cell (CAR-T) therapy manufactured from healthy donor T-cells and available off-the-shelf. These new Phase 1 study subgroup data and a new data analysis of different lymphodepletion regimens in patients treated with P-BCMA-ALLO1 for multiple myeloma or P-MUC1C-ALLO1 for solid tumors are being presented today in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 in San Diego.

"Multiple myeloma remains incurable, and patients often relapse, despite initial high response rates with BCMA-targeted immunotherapies, including autologous CAR-T therapies," said Bhagirathbhai Dholaria, M.D., Associate Professor of Medicine (Hematology/Oncology) at the Vanderbilt-Ingram Cancer Center in Nashville, Tenn. "New treatment options are urgently needed for these patients, which is why I’m encouraged by these impressive Phase 1 subgroup results, which may be the first report of an allogeneic CAR-T therapy showing clinical activity in heavily pretreated patients whose myeloma has progressed after multiple BCMA-targeted immunotherapies."

"These new data build on the P-BCMA-ALLO1 data presented at ASH (Free ASH Whitepaper) 2023, which demonstrated a 100% overall response rate in patients who had not been previously treated with a BCMA-targeted therapy. The new findings also provide additional evidence that our investigational, off-the-shelf allogeneic CAR-T therapy could be an appropriate treatment for a broader range of patients with multiple myeloma, including those with relapsed/refractory disease whose cancer progressed following prior BCMA-targeted therapy, representing the highest unmet need in this setting," said Syed Rizvi, M.D., Chief Medical Officer at Poseida. "In addition, we continue to explore the optimal lymphodepletion regimen for CAR-T in solid tumors and are directly applying these learnings to our P-MUC1C-ALLO1 trial with the goal of delivering the same benefits in solid tumors as we have seen in myeloma. We look forward to sharing more fulsome datasets on both our BCMA and MUC1-C programs in the second half of 2024."

New Phase 1 P-BCMA-ALLO1 Study Subgroup Data

The open-label, multicenter Phase 1 dose-escalation study in patients with relapsed/refractory multiple myeloma is assessing the safety and maximum tolerated dose of P-BCMA-ALLO1 (primary objective) and its anti-myeloma activity (secondary objective). Study participants were required to have received a prior proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody. Five study participants who had progressed on or following prior BCMA-targeting autologous CAR-T, T-cell engagers or both, and with ninety days post-P-BCMA-ALLO1 treatment follow-up, are presented in this poster.

Key findings from the subgroup analysis showed that P-BCMA-ALLO1 was well tolerated with no dose-limiting toxicities, graft vs. host disease, or Grade 3 or greater cytokine release syndrome (CRS) or immune effector cell neurotoxicity syndrome (ICANS). The overall response rate in patients receiving P-BCMA-ALLO1 was 60%, with all three patients who achieved a clinical response experiencing a very good partial response (VGPR). This included one patient who had previously received both teclistamab and an autologous CAR-T therapy and has maintained a response for more than four months.

New Data on Optimizing Lymphodepletion (LD) Regimen for Patients with Solid Tumors Treated with Investigational Allogeneic CAR-T Therapy

As patients with multiple myeloma receive more bone marrow suppressive treatments than those with solid tumors during their treatment journeys, this analysis evaluated the effect of increasing amounts of cyclophosphamide in LD regimens to optimize CAR-T pharmacokinetics.

The analysis compared various LD regimens in two early Phase 1 trials of Poseida’s investigational allogeneic CAR-T cell therapies in patients with multiple myeloma and solid tumors. Results showed that patients with solid tumors may require higher cyclophosphamide doses to achieve adequate LD, which would provide a sufficient niche to support allogeneic CAR-T expansion.

Poster Presentation Details

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Clinical Activity of P-BCMA-ALLO1, a B-cell Maturation Antigen (BCMA) Targeted Allogeneic Chimeric Antigen Receptor T-cell (CAR-T) Therapy, in Relapsed Refractory Multiple Myeloma (RRMM) Patients Following Progression on Prior BCMA Targeting Therapy CT071 Rajesh Belani, M.D., Clinical Development, Poseida Therapeutics Phase I Clinical Trials 1 Monday, April 8, 9:00 a.m.-12:30 p.m. PT Poster section 48, Poster board 21
Solid Tumor Patients Require Higher Cyclophosphamide Dose than Multiple Myeloma Patients to Achieve Adequate Lymphodepletion Necessary to Enable Allogeneic CAR-T Expansion CT070 Sabrina Haag, Ph.D., Translational Medicine, Poseida Therapeutics Phase I Clinical Trials 1 Monday, April 8, 9:00 a.m.-12:30 p.m. PT Poster section 48, Poster board 20
About P-BCMA-ALLO1

P-BCMA-ALLO1 is an investigational allogeneic CAR-T therapy licensed to Roche that targets B-cell maturation antigen (BCMA) and is in Phase 1 clinical development for the treatment of patients with relapsed/refractory multiple myeloma. This allogeneic program includes a VH-based binder that targets BCMA. Phase 1 clinical data presented at ASH (Free ASH Whitepaper) 2023 supports the Company’s belief that TSCM-rich allogeneic CAR-Ts have the potential to offer effective, safe and reliable treatment addressing unmet needs in multiple myeloma. The U.S. Food and Drug Administration granted Orphan Drug Designation to P-BCMA-ALLO1 for the treatment of multiple myeloma. Additional information about the Phase 1 study is available at www.clinicaltrials.gov (NCT04960579).

About P-MUC1C-ALLO1

P-MUC1C-ALLO1 is an investigational allogeneic CAR-T therapy in Phase 1 clinical development for multiple solid tumor indications. Poseida believes P-MUC1C-ALLO1 has the potential to treat a wide range of solid tumors derived from epithelial cells, such as breast, ovarian, colorectal, lung, pancreatic and renal cancers, as well as other cancers expressing a cancer-specific form of the Mucin 1 protein (MUC1-C). P-MUC1C-ALLO1 is designed to be fully allogeneic, with genetic edits to eliminate or reduce both host-vs-graft and graft-vs-host alloreactivity. Poseida has demonstrated the elimination of tumor cells to undetectable levels in preclinical models of both breast and ovarian cancer. Additional information about the Phase 1 study is available at www.clinicaltrials.gov (NCT05239143).

PharmaMar to participate at the 23rd Annual Needham Virtual Healthcare Conference

On April 8, 2024 PharmaMar (MSE:PHM), world leader in the research, development and commercialization of marine-derived anticancer drugs, reported that the Company will participate in the 23rd Annual Needham Virtual Healthcare Conference taking place virtually on April 8-11, 2024 (Press release, PharmaMar, APR 8, 2024, View Source [SID1234641876]).

PharmaMar’s management team, will meet with institutional investors, private equity and venture capital investors, and participate in a fireside chat with Needham’s Research Analyst on April 9th at 08:45 Eastern (14:45 CET).

ORIC Pharmaceuticals Presents Preclinical Data on Two Programs at the 2024 American Association for Cancer Research (AACR) Annual Meeting

On April 8, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported two oral presentations on ORIC-944, a potent and selective allosteric inhibitor of PRC2, and presentation of a new discovery candidate, ORIC-613, an orally bioavailable, potent and selective PLK4 inhibitor, at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, ORIC Pharmaceuticals, APR 8, 2024, View Source [SID1234641875]).

"ORIC-944 in combination with AR inhibitors demonstrates anti-tumor activity in multiple AR-positive prostate cancer models, supporting the planned expansion of our ORIC-944 clinical program in combination with AR inhibitors in metastatic prostate cancer," said Lori Friedman, PhD, chief scientific officer. "These encouraging preclinical findings, coupled with potential best-in-class drug properties and deepened understanding of the mechanism driving synergy, fuel our optimism for advancing this program. Additionally, the unveiling of preclinical characterization of ORIC-613, a potential first- and best-in-class selective PLK4 inhibitor, marks a significant milestone in our discovery program, with preclinical data demonstrating synthetic lethality in TRIM37-high tumors."

Presentation details:

ORIC-944: a potent and selective allosteric inhibitor of PRC2

Discovery of ORIC-944, a novel inhibitor of PRC2 with potential best-in-class properties for the treatment of prostate cancer

ORIC-944, a potent and selective allosteric PRC2 inhibitor with potential best-in-class properties, demonstrates combination synergy with AR pathway inhibitors in prostate cancer models (Presentation will be available on ORIC website on Tuesday, April 9, 2024 at 2:30 p.m. PT)

Key findings of the presentations:

Discovery of ORIC-944 was enabled through structure-based drug design and leveraged a cryptic pocket in an allosteric site in EED, a subunit of PRC2
Comprehensive profiling supports ORIC-944’s best-in-class properties versus competitor PRC2 inhibitors, including PF-06821497, tazemetostat, and CPI-0209:
Strong potency with 106 picomolar EC50 in biochemical binding assay
Superior solubility, oral bioavailability, half-life, and CYP profile in preclinical studies
Clinical half-life estimated at approximately 20 hours, with no sign of CYP autoinduction that is observed with first-generation PRC2 inhibitors
Results from combinations with an AR inhibitor in an in vivo prostate model shows ORIC-944 provides better activity than PF-06821497
Demonstrated that EED and EZH2 inhibitors act through the same mechanism of action, making prostate cancer cells more susceptible to AR inhibition:
Transcriptional changes induced by ORIC-944 were comparable to those of EZH2 inhibitors in prostate cancer models, indicating no mechanistic distinction between molecules targeting different core subunits of PRC2
RNA sequencing of prostate cancer models revealed that ORIC-944 increases AR signaling and luminal cell fate, thereby rendering these cells more susceptible to AR inhibition
Synergy was observed both in vitro and in vivo for ORIC-944 in combination with AR inhibitors in prostate cancer models
These results position ORIC-944 as a potential best-in-class PRC2 inhibitor for combination with AR inhibitors in patients with prostate cancer
ORIC-613: a potent and selective PLK4 inhibitor

ORIC-613, a potential first- and best-in-class, orally bioavailable, potent and selective PLK4 inhibitor with synthetic lethality in TRIM37 high cancer models

Key findings of the presentation:

ORIC-613 is an orally bioavailable, potent and exquisitely selective small molecule inhibitor of PLK4, which is synthetic lethal in tumor cells with high levels of TRIM37
ORIC-613 has superior kinome selectivity versus comparator compounds CFI-400945 and RP-1664
Preclinical assessment in cancer cell lines revealed synthetic lethality, with ORIC-613 inducing apoptotic tumor cell death specifically in TRIM37-high breast cancer and neuroblastoma cells versus TRIM37-wildtype cells
Oral dosing of ORIC-613 at 150 mg/kg QD resulted in tumor regressions and tumor growth inhibition in TRIM37-high xenograft breast tumors
ORIC-613 retained potency in breast cancer models resistant to CDK4/6 inhibitors
These results position ORIC-613 as a potential first- and best-in-class development candidate, which has the potential to benefit patients with TRIM37-high tumors

Mythic Therapeutics Presents Preclinical Data on MYTX-011, an Investigational cMET-Targeting Antibody-Drug Conjugate (ADC), at the American Association for Cancer Research (AACR) Annual Meeting

On April 8, 2024 Mythic Therapeutics, a clinical-stage biotechnology company committed to the development of next-generation antibody-drug conjugate (ADC) therapies for the treatment of a wide range of cancers, reported preclinical data from MYTX-011, its investigational cMET-targeting ADC, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Mythic Therapeutics, APR 8, 2024, View Source;utm_medium=rss&utm_campaign=mythic-therapeutics-presents-preclinical-data-on-mytx-011-an-investigational-cmet-targeting-antibody-drug-conjugate-adc-at-the-american-association-for-cancer-research-aacr-annual-meeting [SID1234641874]).

"Patients with tumors expressing low-to-moderate levels of cMET have not been able to fully benefit from ADC therapies available today, and we continue to be encouraged by the progress made with MYTX-011," said Brian Fiske, Ph.D., Chief Scientific Officer and Co-founder of Mythic. "We previously demonstrated that MYTX-011 drives increased internalization and cytotoxicity in tumor cells expressing moderate cMET levels compared to a matched parent ADC in vitro. This new study adds to our excitement by illustrating how our FateControl technology, incorporated into MYTX-011, enables increased delivery of the ADC’s cytotoxic payload to tumors with moderate cMET expression in vivo. We’re also pleased to present data that highlight the potential of MYTX-011 as a therapeutic candidate for treating multiple types of solid tumors that express cMET."

MYTX-011 is an investigational, pH-sensitive, vcMMAE-based ADC that is designed to benefit not only patients whose tumors express high levels of cMET, but also a broader set of patients whose tumors express low to moderate levels of cMET. MYTX-011 is engineered to rapidly dissociate from cMET only at the acidic pH of endolysosomes.

In studies presented at AACR (Free AACR Whitepaper), the pH-engineered antibody component of MYTX-011 demonstrated markedly increased accumulation in cancer cells expressing high, moderate or low cMET levels compared to its matched non-engineered parent antibody. Consistent with this finding, MYTX-011 demonstrated broader and more potent cMET-dependent cytotoxicity across a panel of cancer cell lines compared to a matched parent ADC. Moreover, in mice bearing NSCLC xenograft tumors with moderate cMET expression, MYTX-011 treatment delivered increased levels of MMAE payload to tumors in vivo as compared to the parent ADC. MYTX-011 was shown to be highly active in cMET+ xenograft models derived from gastric, esophageal and head and neck cancers. Together, these findings provide preclinical proof-of-concept of the potential of MYTX-011 as a therapeutic candidate for treating a broader range of cMET-expressing malignancies.

About MYTX-011

MYTX-011, an investigational cMET-targeting ADC, leverages Mythic’s innovative FateControl technology, which allows antibody-drug conjugates (ADCs) to actively navigate inside of cells, potentially increasing delivery of anti-cancer agents to tumor cells with less impact on healthy cells. This breakthrough approach takes the next step beyond linker-payload technologies and is designed to improve ADC efficacy against a broad set of molecular targets and patient profiles. MYTX-011 is currently being evaluated in the Phase 1 KisMET-01 clinical trial, a first-in-human, open-label, multi-center, dose escalation and dose expansion study enrolling patients with locally advanced, recurrent or metastatic NSCLC (NCT05652868).

Principal Investigator from City of Hope National Medical Center Invited to Present Clinical Data from Marker Therapeutics APOLLO Study at 11th Global Summit on Hematologic Malignancies

On April 8, 2024 Marker Therapeutics, Inc. (Nasdaq: MRKR), a clinical-stage immuno-oncology company focusing on developing next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, reported that Geoffrey Shouse, D.O., Ph.D., the Principal Investigator at City of Hope National Medical Center in Duarte, CA, was invited to present his clinical experience from the APOLLO study at the 11th Global Summit on Hematologic Malignancies in Whistler, BC, Canada (April 2-7, 2024) (Press release, Marker Therapeutics, APR 8, 2024, View Source [SID1234641873]). Dr. Shouse provided an overview on the clinical observations obtained at City of Hope on Saturday, April 6, 2024.

The Phase 1 APOLLO study is investigating MT-601, a multi-tumor associated antigen (multiTAA)-specific T cell product, for the treatment of patients with lymphoma who have failed or are ineligible to receive anti-CD19 chimeric antigen receptor (CAR) T cell therapy. Marker previously reported that the first study participant tolerated the treatment well and achieved a complete response (CR) eight weeks after the second infusion of MT-601, which was maintained at the six months follow-up visit (Press Release, September 11, 2023). During the presentation, Dr. Shouse showed that this study participant remains in CR nine months following initial treatment with MT-601. This APOLLO participant had diffuse large B cell lymphoma (DLBCL) and failed four prior lines of therapy, including anti-CD19 CAR T cell therapy. The participant relapsed within 90 days of CAR T cell therapy yet maintained a CR for at least nine months after treatment with MT-601, suggesting that response to MT-601 was more durable compared to CAR T cells in this study participant.

Dr. Shouse’s presentation included data from two additional study participants that have been treated at City of Hope. One of the study participants had transformed follicular NHL and failed a total of 12 lines of therapy including mosunetuzumab (bispecific antibody) for follicular NHL, and Yescarta (anti-CD19 CAR T cell therapy) after transformation into DLBCL. At the time of MT-601 administration, only follicular NHL persisted after the last treatment. Eight weeks after initial infusion with MT-601, this study participant achieved a CR and remains in CR three months following treatment with MT-601. The third patient treated at City of Hope as part of the APOLLO trial presented with DLBCL with cutaneous involvement only and was not eligible for CAR T cell therapy. When evaluated at eight weeks post-treatment, the study participant was in partial response with all lesions decreasing in size including one that has completely resolved.

Dr. Shouse also reported that treatment was well tolerated among all patients with no significant treatment-related adverse events including no reports of cytokine release syndrome (CRS) or immune-effector cell associated neurotoxicity syndrome (ICANS), and that all patients will continue to be monitored closely for long-term treatment effects and durability of response.

"We are encouraged by these clinical results and the potential impact of MT-601 in patients with lymphoma who have relapsed or are ineligible for CAR T cell therapy," said Geoffrey Shouse, D.O., Ph.D., the Principal Investigator at City of Hope National Medical Center in Duarte, CA. "Observing objective responses in three out of three patients with lymphoma treated with MT-601 at our site is a remarkable and gratifying achievement and we are encouraged by the benefits this therapy has provided to our patients. I am honored to have been invited to showcase these data on MT-601 to leading experts in the field at the 11th Global Summit on Hematologic Malignancies."

The therapeutic potential of MT-601 is further reinforced by non-clinical data demonstrating that MT-601 is able to eradicate lymphoma cells resistant to anti-CD19 CAR T cells (Press Release, May 31, 2023).

CAR T cell therapy is associated with severe adverse events such as cytokine release syndrome or neurotoxicity, as well as the potential risk of inducing secondary cancers (U.S. Food and Drug Administration, November 28, 2023). MultiTAA-specific T cell therapies have been well-tolerated in clinical trials to date. Marker believes that multiTAA-specific T cells represent a safe alternative to CAR T cells due to their non-genetically engineered approach that selectively expands tumor-specific T cells from a patient’s/donor’s blood without the risk of mutagenesis.

"Although treatment with CD19-targeting CAR T cells is rapidly expanding among hematological malignancies, 40-60% of patients relapse within one year of therapy," commented Juan Vera, M.D., President and Chief Executive Officer of Marker Therapeutics. "The sustained CR for nine months in our first study participant, who relapsed 90 days following CAR T cell treatment, indicates durable efficacy of MT-601 versus CAR T cell therapy in this participant."

"Though the number of patients treated to date in our APOLLO study is quite small, observing objective responses in all three study participants treated at City of Hope is encouraging, and highlights the potential benefit of MT-601 in patients with lymphoma. We are continuing to enroll additional patients to hopefully reinforce these promising observations and look forward to treating more participants in this Phase 1 study," concluded Dr. Vera.

About MT-601

MT-601 utilizes a novel non-genetically modified approach that specifically targets six different tumor antigens upregulated in lymphoma cells (Survivin, PRAME, WT-1, NY-ESO-1, SSX-2, MAGEA-4). Marker is currently investigating MT-601 in the Company-sponsored Phase 1 APOLLO trial (clinicaltrials.gov identifier: NCT05798897) for the treatment of lymphoma patients who are relapsed/refractory after or ineligible to anti-CD19 CAR T cell therapies.

About APOLLO

The APOLLO trial (clinicaltrials.gov Identifier: NCT05798897) is a Phase 1, multicenter, open-label study designed to evaluate the safety and efficacy of MT-601 in participants with relapsed or refractory lymphoma who either failed anti-CD19 chimeric antigen receptor (CAR) T cell therapy or are ineligible for anti-CD19 CAR T cell therapy. The primary objective of this exploratory Phase 1 clinical trial is to evaluate the optimum dose, safety, and preliminary efficacy of MT-601 in participants with various lymphoma subtypes. Under the APOLLO trial, it is anticipated that nine clinical sites across the United States will cumulatively enroll up to approximately 30 participants during the dose escalation phase.

About multiTAA-specific T cells

The multi-tumor associated antigen (multiTAA)-specific T cell platform is a novel, non-genetically modified cell therapy approach that selectively expands tumor-specific T cells from a patient’s/donor’s blood capable of recognizing a broad range of tumor antigens. Since multiTAA-specific T cells are not genetically engineered, Marker believes that its product candidates will be easier and less expensive to manufacture, with reduced toxicities, compared to current engineered CAR-T and TCR-based approaches, and may provide patients with meaningful clinical benefits. As a result, Marker believes that its portfolio of T cell therapies has a compelling product profile, as compared to current gene-modified CAR-T and TCR-based therapies.