Poseida Therapeutics Announces FDA Orphan Drug Designation Granted to P-BCMA-ALLO1 for the Treatment of Multiple Myeloma

On March 13, 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 the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for the treatment of multiple myeloma to P-BCMA-ALLO1, a novel BCMA-targeted allogeneic, T stem cell memory (TSCM)-rich chimeric antigen receptor (CAR)-T therapy candidate (Press release, Poseida Therapeutics, MAR 13, 2024, View Source [SID1234641125]). The Company is investigating P-BCMA-ALLO1 in partnership with Roche for the treatment of relapsed/refractory multiple myeloma (RRMM).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The Orphan Drug Designation for P-BCMA-ALLO1 underscores the high unmet medical need for a rapid and accessible off-the-shelf allogeneic CAR-T therapy for patients with multiple myeloma," said Kristin Yarema, Ph.D., President and Chief Executive Officer of the Company. "This designation further validates our belief that TSCM-rich allogeneic CAR-T therapies may potentially offer the optimal combination of clinical results, on-demand availability, and high-volume production, while supporting broader access to CAR-T therapies. We look forward to continuing our work on the Phase 1 study of P-BCMA-ALLO1 and plan to share further clinical updates in 2024."

The Company is currently evaluating P-BCMA-ALLO1 in a Phase 1 clinical trial and recently shared positive early safety and preliminary efficacy data at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2023. Data highlighted at the meeting showed that P-BCMA-ALLO1 was a well-tolerated off-the-shelf therapy with a favorable emerging safety profile, delivered to 100% of patients in the intent-to-treat population with no use of bridging chemotherapy or other anti-myeloma bridging therapies. Preliminary data presented at ASH (Free ASH Whitepaper) also showed allogeneic TSCM-rich CAR-T cells trafficking to bone marrow, differentiating to cell-killing effector T cells and persisting at least 6 weeks after treatment, which support the hypothesis of cell persistence at tumor-relevant sites.

The Company will present data on a subset of recently enrolled patients refractory to initial BCMA targeting therapy in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in San Diego on April 8, 2024, 9:00 AM to 12:30 PM PT.

Subject to coordination with Roche, the Company plans to provide an additional clinical update on the P-BCMA-ALLO1 program at a scientific meeting in the second half of 2024.

The FDA’s Orphan Drug Designation program provides orphan status to drugs or biologics intended for the prevention, diagnosis, or treatment of diseases that affect fewer than 200,000 people in the United States. Sponsors of medicines that are granted Orphan Drug Designation are entitled to certain incentives, including tax credits for qualified clinical trials, prescription drug user-fee exemptions, and potential seven-year marketing exclusivity upon FDA approval.

About P-BCMA-ALLO1

P-BCMA-ALLO1 is an allogeneic CAR-T product candidate licensed to Roche targeting B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma. This allogeneic program includes a VH-based binder that targets BCMA and clinical data presented at ASH (Free ASH Whitepaper) in December 2023 support 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. Additional information about the Phase 1 study is available at www.clinicaltrials.gov using identifier: NCT04960579.

Ryvu Therapeutics Summarizes 2023 Fiscal Year and Provides Corporate Update

On March 13, 2024 Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small-molecule therapies that address emerging targets in oncology, reported its 2023 fiscal year and provides a corporate update (Press release, Ryvu Therapeutics, MAR 13, 2024, View Source [SID1234641124]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Pawel Przewiezlikowski, co-founder, largest shareholder, and Chief Executive Officer of Ryvu Therapeutics, said:

– In 2023, we made significant progress in all key business areas and look forward to multiple catalysts in 2024. We have already started two Phase II studies of RVU120, and around mid-year, we plan to launch two more Phase II studies in hematology. By the end of the year, we plan to enroll more than 100 patients across these clinical trials. We also plan to launch a new Phase II study of MEN1703 (SEL24) in DLBCL, which is being developed under a license agreement with the Menarini Group. Study start-up activities for new trials of both RVU120 and MEN1703 are proceeding quickly.

Krzysztof Brzozka, Ph.D., Executive Vice President, and Chief Scientific Officer, said:

– We are pleased with the significant progress made in our early-phase projects. Among the most advanced projects from our synthetic lethality platform – PRMT5 and WRN – we plan to identify a clinical candidate in 2024. We are also seeing progress in the programs being developed by our partners – particularly BioNTech and Exelixis. We were excited to achieve the second milestone in the Exelixis collaboration, and we look forward to presenting data on our synthetic lethality assets and novel platform at AACR (Free AACR Whitepaper).

2023 SUMMARY AND RECENT CORPORATE EVENTS

RVU120 clinical development plan

In 2023 Ryvu prepared for the launch of two Phase II RVU120 trials, which then initiated in early 2024: 1) RVU120 as monotherapy in genetically defined cohorts of patients with relapsed/refractory acute myeloid leukemia (r/r AML) and high-risk myelodysplastic syndromes (HR-MDS, RIVER-52 study), and 2) RVU120 in combination with venetoclax for patients with relapsed/ refractory AML (RIVER-81 study).
Ryvu will financially support the REMARK study’s Phase II clinical trial of RVU120 in patients with low-risk myelodysplastic syndromes (LR-MDS). REMARK will be conducted as an investigator-initiated study through the EMSCO network, with Prof. Uwe Platzbecker, a globally renowned expert in the field of LR-MDS, as the Coordinating Principal Investigator. Start-up activities have already been launched, and patient enrollment will start in mid-2024.
Study start-up is also underway for POTAMI-61, a Phase II study evaluating the efficacy of RVU120 in patients with myelofibrosis (MF). Initiation of patient recruitment is scheduled for mid-2024.
Translational research on RVU120 in solid tumors will continue, including combination studies, as well as academic collaborations in the areas of medulloblastoma (MB) and sarcoma-related research.
The company plans to enroll more than 100 patients across all RVU120 Phase II trials this year and aims to present initial Phase II data by the end of 2024.
RVU120’s updated clinical development plan includes studies (RIVER-52, RIVER-81, and POTAMI-61) that could lead to three drug approvals between 2026 and 2027.
Key data presented during 2023 conferences

In 2023, Ryvu Therapeutics presented data from the RVU120 program at several international conferences, including EHA (Free EHA Whitepaper) 2023, ESMO (Free ESMO Whitepaper) 2023, and ASH (Free ASH Whitepaper) 2023:

RVU120 monotherapy demonstrated clinical activity in a Phase Ib study in which 50% of evaluable patients with r/r AML or HR-MDS achieved clinical benefit, including a complete response, morphologically leukemia-free status, clinically significant reduction of blasts including reductions that allowed bridging to a bone marrow transplantation, two-year disease stabilization, hematologic improvements, as well as reduction in bone marrow fibrosis.
In particular, early signs of efficacy were observed in patients with an NPM1 mutation, DNMT3a mutation, and HR-MDS.
The recommended Phase II dose (RP2D) of 250 mg was found to be safe and well-tolerated, achieving RVU120 concentrations in the pharmacologically active range, with a level of target inhibition between 50% and 70%. This level of target inhibition is expected to result in therapeutic efficacy in selected patients or in combinations with synergistic therapies.
RVU120 is emerging as a potential candidate in the first-line treatment of AML, supported by its activity against leukemic stem cells.
RVU120 acts synergistically with venetoclax in both sensitive and venetoclax-resistant models.
At the ENA conference in October 2023, Ryvu presented preclinical data for PRMT5 and the synthetic lethality platform, and Ryvu’s partner – Menarini Group, presented preclinical data for MEN1703 in advanced diffuse large B-cell lymphoma (DLBCL).

Ryvu has developed potentially best-in-class MTA-cooperative PRMT5 inhibitors with outstanding drug-like physicochemical properties and the ability to block methyltransferase activity of PRMT5 with nanomolar concentrations and bioavailable upon oral administration. The novel, optimized inhibitors exhibit a significantly improved pharmacokinetic profile. In addition, the compounds show antitumor efficacy and target engagement in vivo, providing a solid foundation for further development towards clinical trials.
MEN1703 (SEL24) has shown promising antitumor activity in translational studies in various types of DLBCL. These data justify the development of MEN1703 in Phase II clinical trials in this indication.
Expansion of MEN1703 (SEL24) development by Ryvu’s partner – Menarini Group, to include a new Phase II clinical trial in DLBCL.

In September 2023, Ryvu announced the Menarini Group’s decision to expand the development of MEN1703 (SEL24) by initiating a new Phase II clinical trial in patients with DLBCL.

A Phase II study in DLBCL is scheduled to begin in mid-2024. The goal is to evaluate the activity of MEN1703 (SEL24) as monotherapy and in combination with standard therapy in patients with DLBCL.
The study will be initiated based on the potent activity of MEN1703 (SEL24) observed in preclinical lymphoma models. Clinical trials have confirmed the acceptable safety profile and early signs of activity of MEN1703 (SEL24) as a monotherapy. Based on the available data, further program development will continue in patients with DLBCL and potentially in additional indications.
Recent financial events

On February 3, 2024, Ryvu received notice that the second financial milestone was achieved under the collaboration agreement with Exelixis, resulting in a $2M payment to Ryvu. Ryvu and Exelixis are working under a research collaboration and license agreement to develop antibody-drug conjugates (ADCs) with Ryvu’s portfolio of STING agonists.
On March 5, 2024, Ryvu received notice from the European Investment Bank (EIB) that it had met the conditions for disbursement of the first venture debt tranche of €8M. These funds are not yet included in the cash balance reported in this press release, but Ryvu expects to receive the funds on March 13, 2024. As part of the agreement announced in August 2022, Ryvu still has access to an additional €14M in venture debt from the EIB.
UPCOMING EVENTS

Ryvu will attend the AACR (Free AACR Whitepaper) Annual Meeting (San Diego, USA) from April 5-10, 2024, to present preclinical data from its synthetic lethality pipeline, RVU120, and MEN1703 (SEL24).
2023 Fiscal Year Financial Update[1]

Cash Position – On December 31, 2023, Ryvu Therapeutics held $63.7M in cash, cash equivalents, and bonds, compared to $23.2M at the end of 2022. On March 7, 2024, Ryvu Therapeutics held $57.2M in cash, cash equivalents, and bonds, which excludes €8M in venture debt from the EIB to be received imminently.

Operating Revenues – In 2023, Ryvu recognized total operating revenues (including grants) of $16.3M, compared to 2022, when the total operating revenue amounted to $15.8M.

Operating costs, excluding the non-cash cost of valuation of the Incentive Program ($2.0M) and valuation of NodThera shares ($0.9M) in the full year 2023, amounted to $37.6M, representing an increase compared to $26.4M in the previous year.

Net Loss Attributable to Common Shareholders – In 2023, the net loss attributable to common shareholders, excluding the non-cash cost of valuation of the Incentive Program, amounted to $20.0M, compared to $13.8M in the previous year.

Caris Life Sciences to Showcase Research at 2024 SGO Annual Meeting on Women’s Cancer

On March 13, 2024 Caris Life Sciences(Caris), the leading next-generation AI TechBio company and precision medicine pioneer that is actively developing and delivering innovative solutions to revolutionize healthcare and improve the human condition using molecular science and AI, reported that the company and collaborators within the Caris Precision Oncology Alliance (POA) will collectively present three studies across multiple gynecological tumor types at the 2024 SGO Annual Meeting on Women’s Cancer, March 16-18, 2024, in San Diego (Press release, Caris Life Sciences, MAR 13, 2024, View Source [SID1234641123]). The findings demonstrate the power of Caris’ comprehensive multi-modal database, generated by examining every gene, to enable novel insights into cancer that could have profound effects on a patient’s diagnosis, prognosis, care plan and response to treatment.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are proud to return and present an array of precision oncology research at this year’s SGO Annual Meeting. The findings represent important observations in various gynecological malignancies, including the effect of molecular subtype on survival in uterine carcinosarcoma, identification of potential prognostic biomarkers in ovarian cancer, and an exploration of the frequency and outcomes of endometrial tumors with alterations in multiple molecular classifiers," said Caris EVP and Chief Medical Officer George W. Sledge, Jr., MD. "We are confident that Caris’ powerful comprehensive molecular profiling, matched clinical outcomes data and in-depth collaborative efforts within our POA member institutions will lead to novel insights into cancer biology, new targeted therapies and ultimately improved outcomes for all patients with gynecological cancers."

Survival outcomes according to molecular classification of uterine carcinosarcoma
Walking Poster Session | Walking Poster Group 5: Cancer Care Delivery
March 17: 8:15 – 8:45 AM PST

Uterine carcinosarcoma (UCS) is an aggressive cancer with a poor prognosis, yet there are limited studies evaluating its molecular subtypes and their association with survival outcomes. In this new study, more than 4,000 UCS and endometrioid endometrial cancer (EEC) tumors were evaluated using next-generation sequencing (NGS) to determine if UCS molecular subtype governs survival. This is the first study to report survival outcomes according to molecular classification in UCS compared to an EEC cohort.

Frequency and outcomes of co-mutations according to ProMisE classifiers in endometrial cancer
Poster Session I
March 17: 1:15 – 1:45 PM PST

The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) criteria classify four molecular subtypes of endometrial tumors (ET). However, there is limited understanding of how the presence of alterations in multiple classifiers affects ET prognosis. Whole exome sequencing of over 5,100 ETs revealed that some ETs have overlapping molecular subtypes.
Molecular characterization of squamous cell ovarian cancers for identification of therapeutic targets
Poster Session I
March 17: 1:15 – 1:45 PM PST

Not all ovarian cancers have the same prognosis; ovarian squamous cell carcinoma (OSCC), for example, is associated with a worse prognosis than high-grade serous ovarian cancer (HGSOC). Through NGS of DNA and RNA from ovarian tumors (OSCC, HGSOC, and Brenner’s tumors), this study sought to identify prognostic factors and molecular markers associated with OSCC. High tumor mutational burden (TMB) and lack of ER, PR expression were found to be molecular characteristics of OSCC, along with other distinct patterns of molecular and immune markers. Further characterization of OSCC may lead to the identification of therapeutic targets.
Poster and abstract summaries highlighting the Caris research presented at SGO 2024 will be available onsite at Caris’ booth (#601). The full abstracts will be available on the Caris website beginning on March 16.

The POA includes 91 cancer centers, academic institutions, research consortia and healthcare systems, including 43 NCI-designated cancer centers, collaborating to advance precision oncology and biomarker-driven research. POA members work together to establish and optimize standards of care for molecular testing through innovative research focused on predictive and prognostic markers that improve the clinical outcomes for cancer patients.

Aadi Bioscience Announces Financial Results for the Fourth Quarter and Full-Year 2023 and Provides Corporate Update

On March 13, 2024 Aadi Bioscience, Inc. (NASDAQ: AADI), a commercial-stage, precision oncology company focused on developing and commercializing therapies for cancers with alterations in the mTOR pathway, reported financial results for the fourth quarter and full-year ended December 31, 2023, and highlighted recent corporate progress (Press release, Aadi Bioscience, MAR 13, 2024, View Source [SID1234641122]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"With strong execution against our commercial and development goals, 2023 was a year of progress and momentum for Aadi," said Dave Lennon, President and CEO of Aadi Bioscience. "As the preferred treatment for malignant PEComa, FYARRO saw significant growth and high penetration in academic and community settings. Clinically, we were encouraged by the interim results from the registration-directed PRECISION1 trial, and look forward to the two-thirds readout expected in Q3. We also initiated enrollment of two Phase 2 trials in what we believe are promising mTOR-driven cancer targets, endometrial cancer and neuroendocrine tumors, as we further characterize the potential of nab-sirolimus. With a commercial foundation, bold development vision and solid cash runway in to Q4 2025, we believe we are well-positioned to realize our ambition of becoming a multi-indication precision oncology company."

Recent Operational Highlights

FYARRO net product sales were $6.3 million in the fourth quarter, or 21% growth over the prior year period, and $24.4 million for full-year 2023, representing 60% growth year-over-year.
PRECISION1 on track to complete enrollment by May 2024, with the two-thirds interim analysis expected in Q3 2024. Early data presented in December 2023 demonstrated sustained tumor reductions in heavily pre-treated population from investigator-assessed responses in first 40 patients across both arms. The safety profile was consistent with the nab-sirolimus label and the mTOR inhibitor drug class.
Enrollment of two single-indication Phase 2 trials underway to investigate the potential of nab-sirolimus for difficult-to-treat mTOR-driven cancers: neuroendocrine tumors (NETs), and advanced or recurrent endometrioid-type endometrial cancer (EEC) in combination with letrozole.
NETs are rare, ~3,500 cases a year, with low response rates to existing recommended treatments. Preclinical models indicate improved target suppression relative to other mTORs in the NETS population.
Endometrial cancer is the most common cancer of the female reproductive organs and one of the few cancers with increasing mortality. There are an estimated 10,000 cases of EEC diagnosed annually. Prior clinical studies with mTOR inhibitors and letrozole have yielded promising results in EEC.
Fourth Quarter and Full-year 2023 Financial Results

Cash, cash equivalents and short-term investments as of December 31, 2023, were $108.8 million as compared to $172.6 million as of December 31, 2022, which is expected to fund operations into Q4 2025 based on current plans.
Total revenue for the quarter ended December 31, 2023, was $6.3 million, and $24.4 million for the full-year ended December 31, 2023, resulting from sales of FYARRO.
Net loss for the three months ended December 31, 2023, was $16.3 million as compared to $13.9 million for the three months ended December 31, 2022. Net loss for the full-year ended December 31, 2023, was $65.8 million, as compared to $60.5 million for the same period in 2022.
Conference Call Information

The Aadi management team is hosting a conference call and webcast today at 8:30 am EDT (5:30 am PDT) to provide a corporate update and discuss results for the fourth quarter and full-year 2023.

Participants may access a live webcast of the call on the "Investors & News" page of the Aadi Bioscience website at aadibio.com. To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the Company’s website for at least 30 days.

Kazia announces presentation of new data at AACR Annual Meeting

On March 13, 2024 Kazia Therapeutics Limited (NASDAQ: KZIA), a biotechnology company specialising in oncology, reported the presentation of new data for both its pipeline molecules, paxalisib and EVT801, at the upcoming Annual Meeting of the American Association of Cancer Research (AACR) (Free AACR Whitepaper) in San Diego, California, from 5-10 April 2024 (Press release, Kazia Therapeutics, MAR 13, 2024, View Source [SID1234641121]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

There will be three presentations in total at AACR (Free AACR Whitepaper), including data from the phase 1 study of EVT801 in advanced solid cancers. The data being presented will outline initial clinical data from the phase 1 study and provides support and direction for the next stage of the study.

In addition, data will be presented on the results of the combination therapy of paxalisib and gemcitabine for patients with relapsed/recurrent atypical teratoid/rhabdoid tumors AT/RT. Based on these findings, the Pacific Pediatric Neuro-Oncology Consortium (PNOC) is planning to include this therapy in its next AT/RT international clinical trial.

Summary of Abstracts

Session PO.CL01.15 – Early Detection Biomarkers 1
April 7, 2024 – 1:30pm-5:00pm
Abstract 1059 / 7: Biomarkers analysis on samples from patients in EVT801 clinical trial: Patient characterization and immunomonitoring
L. Davenne, M. Fitzgerald, P.-B. Ancey, O. Delpuech, C. Poussereau-Pomié, M. Esquerre, M. R. Paillasse, M. Mandron, P. Rochaix, M. Ayyoub, C. Scarlata, C. Caux, P. Cassier, C. Gomez-Roca, J.-P. Delord, J. Friend, P. Fons
Evotec International GmbH, Toulouse, France, Kazia Therapeutics, Sydney, Australia, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France, Centre Léon Bérard, Lyon, France

Session PO.CTP01.01 – Phase I Clinical Trials in Progress 1
April 8, 2024 – 9:00am-12:30pm
Abstract CT088 / 15: EVT801, a novel selective VEGFR-3 inhibitor targeting tumor angiogenesis, is pursuing dose escalation stage of phase I first-in-human study

C. Gomez-Roca, P. Cassier, M. Fitzgerald, L. Davenne, C. Costantin, P. Rochaix, J.-P. Delord, J. Friend, A. Nizzardo, A. Tagliavini, M. Pergher, P. Fons, M. Mandron
Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France, Centre Léon Bérard, Lyon, France, Kazia Therapeutics, Sydney, Australia, Evotec International GmbH, Toulouse, France, Evotec International GmbH, Verona, Italy

Session MS.CL08.01 – Novel Approaches for Targeted Therapies
April 9, 2024 – 2:50pm-3:05pm
Abstract 6565 – Improving survival of atypical teratoid/rhabdoid tumor orthotopic xenografts through the combination of PI3K inhibitor paxalisib and nucleoside analog gemcitabine

T. Findlay, K. Malebranche, A. Geethadevi, C. Eberhart, J. Rubens, E. Raabe
Johns Hopkins University School of Medicine, Baltimore, MD