On April 8, 2024 Notable Labs, Ltd. (Nasdaq: NTBL) ("Notable" or the "Company"), a clinical-stage precision oncology company developing a new class of cancer therapies identified by its Predictive Precision Medicine Platform (PPMP), reported data related to innovations in the use of cryopreserved samples in the PPMP assay at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR 2024) being held in San Diego, CA (Poster abstract 2548) (Press release, Notable Labs, APR 8, 2024, View Source [SID1234641885]).

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"We are very pleased to share the result of our innovative sample handling study with the cancer community at AACR (Free AACR Whitepaper) 2024. The ability to derive a high-quality assessment of the response to treatment based on the results of cryopreserved samples is an important innovation. It has been previously thought that frozen samples could not be effectively thawed and used for cell viability assays. Based on the data presented at AACR (Free AACR Whitepaper), Notable now has the potential to develop partnerships to assess new treatment regimens, including combination therapies, using Notable’s PPMP platform and archived, cryopreserved samples thawed according to our protocols and proprietary media compositions," said Thomas Bock, M.D., Chief Executive Officer of Notable. "We hope this opens new opportunities to apply our PPMP to a broad range of archived samples and therapeutics to unlock value and new treatment options for patients with cancer."

Joseph Wagner, Ph.D., Chief Scientific Officer of Notable, added, "As we are ready to initiate the Phase 2 program with volasertib in Q2 2024, we are dedicated to maintaining a focus on innovation for our PPMP. The careful evaluation of sample handling protocols, presented at AACR (Free AACR Whitepaper) 2024, makes our PPMP more comprehensive and enhances the opportunity to study and apply it more broadly. As we continue to execute, we look forward to further demonstrating the potential of PPMP and partner with biopharmaceutical companies and innovators to provide potential new treatment options for patients with cancer."

Summary of Data and Findings for Notable’s Sample Handling Study:

Overview: The study was designed to evaluate the potential use of cryopreserved samples as an alternative to fresh samples for predicting treatment response in acute myeloid leukemia (AML) using Notable’s PPMP.

● Cryopreserved samples are known for exhibiting low sample viability and cell recovery, rendering their practical utilization challenging
● Notable adapted an existing methodology to process cryopreserved patient-derived leukemia cells to investigate their use as an alternative to fresh samples in the PPMP assay

Method: First, a method was established using freshly isolated white blood cells (WBCs) from AML patients (<2 days from sample collection). A fraction of these cells was cryopreserved. Both fresh and cryopreserved cells (after thawing and culturing) were assessed on the PPMP and results compared. Second, the established method was applied to cryopreserved samples (from a biobank) collected from AML patients prior to their treatment with chemotherapy (cytarabine plus idarubicin). Results obtained on the PPMP were compared to the clinical responses experienced by the patients after treatment with cytarabine and idarubicin.

Results: For the method development study, ex vivo responses to 3 different compounds (venetoclax, 5-azacytidine and decitabine) were assessed after culturing of the cryopreserved cells for 24- and 48-hour post thaw using two different media ("A" and "B"). There was a strong correlation (R2 from 0.77 to 0.92) for venetoclax and 5-azacytidine between the results obtained with fresh vs. frozen samples. For the biobank samples treated with cytarabine and idarubicin, culture media A and B show a similar dose-response behavior. Importantly, the PPMP correctly predicted clinical responders (complete remission) and non-responders (refractory).

While Notable will continue to evaluate and validate these sample handling methodologies, these data open the door to the use of cryopreserved samples from retrospective cohorts.

Poster information: Retrospective prediction of clinical response to standard-of-care therapies in acute myeloid leukemia by an ex vivo drug sensitivity assay using cryopreserved primary samples

Session Category: Clinical Research

Session Title: Real-World Biomarkers

Session Date and Time: Monday Apr 8, 2024 9:00 AM – 12:30 PM PT

Location: Poster Section 45

Poster Board Number: 8

Published Abstract Number: 2548

The full poster will be posted to the company’s website in the Scientific Presentations & Publications page in the Investors section of the website shortly after the event.

On April 8, 2024 Theratechnologies Inc. ("Theratechnologies" or the "Company") (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported preclinical data that highlight the versatility and flexibility of the Company’s SORT1+ Technology platform (Press release, Theratechnologies, APR 8, 2024, View Source [SID1234641884]). In a poster session at the 2024 annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in San Diego, Calif., researchers reported that Theratechnologies’ investigational camptothecin-peptide conjugates are well tolerated and associated with significant tumor regression in colorectal cancer (CRC) and triple-negative breast cancer (TNBC) xenograft models. The study also demonstrated synergistic anti-tumor efficacy and good tolerability with the combination of two peptide drug conjugates with different payloads.

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"The preclinical data presented at AACR (Free AACR Whitepaper) add to the sizeable body of evidence supporting the potential utility of the SORT1+ Technology platform as an engine for the development of novel peptide-drug conjugates to treat various types of cancer," said Christian Marsolais Ph.D., Senior Vice President and Chief Medical Officer at Theratechnologies. "In addition to our lead peptide-drug conjugate, sudocetaxel zendusortide, these latest data highlight the promising tolerability and anti-tumor effects of our investigational camptothecin-peptide conjugates, further demonstrating the versatility and flexibility of the platform. We welcome discussions with potential partners who are interested in the further development of these innovative therapies."

The SORT1+ Technology platform relies on the use of a novel, proprietary peptide called TH19P01, which can be conjugated (attached) to numerous well-characterized anticancer drugs. Theratechnologies designed TH19P01 to interact with and be transported by the scavenger receptor sortilin (SORT1), which is involved in protein internalization, sorting, and trafficking, and is expressed in multiple tumor types. Targeting SORT1 with platform-derived peptide-drug conjugates (PDCs) leads to receptor-mediated internalization (endocytosis) of anticancer agents. Once inside cancer cells, active drug is released from the peptide and exerts its cytotoxic effect directly on the cancer cell.

In the poster presented at AACR (Free AACR Whitepaper), the investigators noted that SORT1 gene silencing inhibits camptothecin-conjugate uptake in human HT-29 colorectal adenocarcinoma cells. This observation suggests that these PDCs enter cancer cells via a SORT1-mediated internalization process.

The investigators also described the preclinical effects of three PDCs – TH2101, TH2205, and TH2310 – that have a cytotoxic payload of SN-38, the active metabolite of irinotecan, an anticancer agent that is derived from the Chinese tree Camptotheca acuminate. In addition, the poster summarized the activity of another PDC, TH2303, which carries an exatecan payload, a structural analog of camptothecin. Compared to unconjugated irinotecan, the exatecan- and SN-38-conjugates exerted greater anti-proliferative activities against CRC cells in mice. In two different CRC xenograft models, as well as in the TNBC xenograft model, TH2303 was associated with increased tumor growth inhibition and greater tolerability compared to unconjugated exatecan or irinotecan.

In another experiment described in the poster, the combination of two SORT1-targeting PDCs – sudocetaxel zendusortide (TH1902) and TH2101, which have a synergistic anti-tumor effect at reduced doses, led to increased tumor growth inhibition and some complete responses in the HT-29 xenograft model, compared to either PDC administered alone. The combination also was well tolerated.

"The significant tumor regression following combination therapy is notable because the HT-29 xenograft model is known for its resistance to multiple cytotoxic drugs," commented Prof. Borhane Annabi, Chair in Cancer Prevention and Treatment in the Chemistry Department at the Université du Québec à Montréal. "That observation, along with the impressive anticancer efficacy of the camptothecin-peptide conjugates when administered alone, underscores the potential feasibility of this approach in treating various tumor types."

A copy of the AACR (Free AACR Whitepaper) poster, as well as a second poster presented at the conference, which reinforces existing data for the Company’s lead investigational PDC sudocetaxel zendusortide (TH1902) in activating anti-PD-L1 immunotherapy tumor cell-killing in SORT+1 cancers, can be found at the Theratechnologies website.

About Sudocetaxel Zendusortide (TH1902) and SORT1+ Technology

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

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

On April 8, 2024 Syndax Pharmaceuticals (NASDAQ: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported the presentation of positive data from the pivotal AUGMENT-101 trial in pediatric patients with relapsed/refractory (R/R) KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) treated with revumenib, a first-in-class menin inhibitor (Press release, Syndax, APR 8, 2024, View Source [SID1234641883]). The pediatric data was featured in a Plenary Session titled "Pivotal Phase 2 Results of AUGMENT-101 for Revumenib in KMT2Ar Acute Leukemia: Pediatric Experience" at the 2024 American Society of Pediatric Hematology/Oncology (ASPHO) Conference held April 3 – 6, 2024 in Seattle, Washington.

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"We are pleased to present positive results from pediatric patients treated with revumenib in the AUGMENT-101 pivotal trial demonstrating impressive activity and consistency with the adult population," said Neil Gallagher, M.D., Ph.D., President, Head of Research and Development at Syndax. "As the only menin inhibitor with a formulation designed for the pediatric setting, we have an ongoing commitment to bringing this first- and best-in-class therapeutic agent to this important patient population in need of effective treatments."

The presented data include efficacy and safety findings for pediatric patients with R/R KMT2Ar acute leukemia from the pivotal Phase 2 portion of the AUGMENT-101 study. Of the 57 patients enrolled in AUGMENT-101 with central confirmation of their KMT2Ar status and sufficient follow-up to be included in the efficacy-evaluable population, 13 (23%) were less than 18 years old with a median age of 5 years. The pediatric patients were heavily pretreated with a median of 4 prior lines of therapy including 8 (62%) that received prior venetoclax, 2 (15%) that received CAR-T and 6 (46%) that received prior hematopoietic stem cell transplant (HSCT).

In this population, the complete remission (CR) or CR with partial hematological recovery (CRh) rate was 23% (3/13; 95% CI: 5.0, 53.8), with a median time to CR or CRh of 2.3 months (95% CI: 1.0, 3.9). The overall response rate1 was 46% (6/13), and the composite response rate2 (CRc) was 39% (5/13). Sixty percent (3/5) of CRc patients achieved minimal residual disease negative status. The median overall survival was 6.9 months (95% CI, 2.3–not reached). Four (67%) of the 6 patients who achieved an overall response underwent HSCT, two of whom did not achieve a CR or CRh prior to transplant. Half (2/4) of the patients who underwent HSCT received post-transplant maintenance with revumenib and had been in remission for 6 and 9 months at the time of the July 24, 2023 data cutoff.

Revumenib was well-tolerated, and the safety profile was consistent with the Company’s previously reported data. In the safety-evaluable patient population, Grade 3 or greater treatment-related adverse events that occurred in greater than 10% of patients included febrile neutropenia (13%; 3/23) and decreased neutrophil count (13%; 3/23). Grade 3 or greater differentiation syndrome was observed in 9% (2/23) of patients and Grade 3 QTc prolongation was observed in 4% (1/23) of patients. No treatment-related discontinuations or dose reductions due to adverse events occurred in the trial.

A copy of the presentation is available in the Publications and Meeting Presentations section of Syndax’s website.

About Revumenib

Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged, also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and NPM1-mutant AML. Positive topline results from the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint with a CR/CRh rate of 23% (13/57; 95% confidence interval [CI]: [12.7, 35.8, one-sided p-value = 0.0036]) were presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Data from the Phase 1 portion of AUGMENT-101 in acute leukemia was published in Nature. Revumenib was granted Orphan Drug Designation by the FDA and European Commission for the treatment of patients with AML, and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted Breakthrough Therapy Designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement. The New Drug Application (NDA) for revumenib for the treatment of adult and pediatric R/R KMT2Ar acute leukemia was granted Priority Review by the FDA with a Prescription Drug User Fee Act target action date of September 26, 2024, under the Real-Time Oncology Review Program.

About AUGMENT-101

AUGMENT-101 is a Phase 1/2 open-label trial designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of orally administered revumenib. The Phase 1 dose escalation portion of AUGMENT-101 included two cohorts based on concomitant treatment with a strong CYP3A4 inhibitor. Arm A enrolled patients not receiving a strong CYP3A4 inhibitor, while Arm B enrolled patients receiving a strong CYP3A4 inhibitor. The Phase 2 pivotal portion of AUGMENT-101 has enrolled R/R patients across the following trial populations: patients with mNPM1 AML, patients with KMT2Ar AML, and patients with KMT2Ar ALL. The primary endpoint for each of the cohorts is efficacy as measured by complete remission rate (CR + CRh) per protocol, with secondary endpoints including duration of response and overall survival (OS). Positive data from the pivotal AUGMENT-101 trial of revumenib in adult and pediatric patients with KMT2Ar AML and ALL served as the basis for the NDA submission that is currently under review by the FDA. Enrollment has been completed in the AUGMENT-101 pivotal trial cohort of patients with R/R mNPM1 AML and topline data is expected in the fourth quarter of 2024.

About KMT2A (MLL) Rearranged Acute Leukemia

Rearrangements of the KMT2A (mixed lineage leukemia or MLL) gene give rise to KMT2Ar acute leukemia that is known to have a poor prognosis. KMT2A genes produce fusion proteins that require interaction with the protein called menin to drive leukemic cancer growth. Disruption of the menin-KMT2Ar interaction has been shown to halt the growth of KMT2Ar leukemic cells. KMT2Ar acute leukemia can phenotypically appear as AML, ALL, or mixed phenotype acute leukemia (MPAL) and is routinely diagnosed through currently available cytogenetic or molecular diagnostic techniques. The median overall survival (OS) after standard of care first-line treatment, including intensive chemotherapy and transplant, is less than one year and the majority of patients suffer relapse within five years. With third line treatment or beyond, less than 5% of patients achieve complete remission, and the median OS is less than three months. There are currently no approved therapies indicated for KMT2A-rearranged acute leukemia.

On April 8, 2024 Syncromune Inc., a clinical-stage biopharmaceutical company focused on the development of SYNC-T, an in situ personalized therapy optimized for solid tumor cancers, reported the presentation of positive results from the SV-102 Phase 1 trial at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 (Press release, Syncromune, APR 8, 2024, View Source [SID1234641882]). The trial, involving patients with metastatic castrate-resistant prostate cancer
(mCRPC), showed an overall response rate (ORR) of 85%.

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James Armitage, M.D., Chairman of Syncromune’s Scientific Advisory Board, former President of ASCO (Free ASCO Whitepaper) and Joe Shapiro Professor of Medicine at the University of Nebraska Medical Center, commented on the results stating, "This is an innovative and exciting new therapeutic approach that shows promise with encouraging results in treating mCRPC. With minimal toxicity and high response rates in this debilitating cancer, SYNC-T holds significant potential as a viable treatment option for patients with mCRPC. I am incredibly eager to see how it progresses in future clinical trials."

SYNC-T is a novel and personalized in situ therapy that uses a combination of partial tumor lysis and intratumoral immunotherapy. First, lysis is performed via freezing to disrupt a portion of a target tumor which facilitates the release of cancer-specific signals and activation of the immune system, after which a fixed-dose multi-target drug, SV-102, is directly administered into the tumor site. This is intended to further stimulate the immune system and block mechanisms that suppress the immune response. This combination approach is intended to empower the immune system to recognize and attack patient-specific cancer throughout the body. Injecting SV-102 directly into
the tumor enables significantly smaller doses in comparison to those required for systemic IV administration, which may contribute to fewer side effects and lower toxicity than current therapies.

George Prendergast, Ph.D., President and CEO of the Lankenau Institute for Medical Research (LIMR), part of Main Line Health, and former Editor-in-Chief of the AACR (Free AACR Whitepaper)’s flagship journal, Cancer Research, added, "This rate of clinical response in mCRPC is unprecedented, given it is a disease with few treatment options, high mortality rates, and for which current treatments have exhibited low response rates and high toxicity. Remarkably, one subject in the trial who enrolled with more than 50 metastatic bone lesions and significantly advanced disease experienced a complete response. This is a profound outcome given the subject’s advanced bone metastases. Based on the clinical data and our observations to date, SYNC-T is emerging as a first-in-class therapy that warrants continued clinical trials."

The Phase 1 trial enrolled 15 mCRPC subjects, most of whom had diffuse bone metastases and had experienced failure with prior therapies. Subjects received SYNC-T therapy with the SV-102 multitarget biologic drug every four weeks for up to 12 cycles with response evaluation every eight weeks. SYNC-T demonstrated an ORR of 85% with five complete responses (CRs) and six partial responses (PRs) among the 13 evaluable subjects. The treatment was well tolerated, with minimal side effects and no significant safety concerns. The trial is ongoing, with results expected in the second half of 2024.

These encouraging results support the continued clinical development of the SYNC-T Therapy platform to potentially offer a new treatment option for patients with mCRPC and other solid tumors. The trial’s inclusion in AACR (Free AACR Whitepaper)’s press program highlights the interest of the oncology research community in these findings.

For more information about Syncromune and its ongoing clinical trials, please visit
www.syncromune.com.

On April 8, 2024 Shorla Oncology (‘Shorla’), a U.S.-Ireland specialty pharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has accepted for review the company’s New Drug Application (NDA) for SH-201, the first palatable oral liquid of the related chemotherapeutic agent to treat certain forms of leukemia and other cancers (Press release, Shorla Oncology, APR 8, 2024, View Source;utm_medium=rss&utm_campaign=shorla-oncology-announces-fda-filingacceptance-of-new-drug-application-to-treatcertain-forms-of-leukemia-and-other-cancers [SID1234641881]). The Agency assigned a Prescription Drug User Fee Act ("PDUFA") action date of November 30, 2024.

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"With this NDA acceptance for SH-201, we are a step closer to providing an alternative treatment to thousands of U.S. patients diagnosed with leukemia and other cancers who do not currently have the option of an oral liquid," said Sharon Cunningham, Chief Executive Officer and Co-Founder of Shorla Oncology.
"Submitting this drug to the FDA for review is more than just a milestone for our company, it’s an important moment for all those impacted by this disease including patients, caregivers and clinicians."
SH-201 is an oral liquid treatment that slows or stops the growth of certain forms of leukemia and other cancers such as:

*Chronic Myeloid Leukemia – Affects approximately 9,280 new patients each year in the U.S.1
*Acute Lymphoblastic Leukemia – Impacts approximately 6,550 new patients each year in the U.S.2

"The FDA’s action today ensures that Shorla is well positioned to bring this innovative oral drug to market," said Orlaith Ryan, Chief Technical Officer and Co-Founder of Shorla Oncology. "SH-201 addresses key areas of unmet need by providing a palatable liquid treatment option for patients suffering with cancer."
This milestone for SH-201 follows acceptance to file announced in January of this year for SH-105, a novel, differentiated ready-to-dilute formulation for the treatment of adenocarcinoma of the breast or ovary. It is progressing through FDA review. The company recently raised $35 million in Series B funding that has allowed Shorla to accelerate the growth of its oncology portfolio. Last year, the company launched Nelarabine for the treatment of T-cell Leukemia and JYLAMVO, the first and only oral methotrexate solution approved in the United States for use in adults for the treatment of acute lymphoblastic leukemia and other indications.

About SH-201
SH-201 is the first palatable oral liquid of the related chemotherapeutic agent in the U.S. SH-201 is an oral liquid treatment that slows or stops the growth of certain forms of leukemia (such as acute lymphoblastic leukemia and chronic myeloid leukemia) and other cancers.