On September 16, 2021 Ayala Pharmaceuticals, Inc. (NASDAQ: AYLA), a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare and aggressive cancers, reported new preliminary clinical data from the 6mg cohort of its ongoing Phase 2 ACCURACY trial of AL101 for the treatment of recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) harboring Notch-activating mutations (Press release, Ayala Pharmaceuticals, SEP 16, 2021, View Source [SID1234593999]). The data is being presented at the 2021 ESMO (Free ESMO Whitepaper) Virtual Congress as an ePoster. In a separate ePoster presentation, Ayala presented new preclinical results evaluating the potential of AL101 in combination with approved cancer therapies for dual targeting of ACC tumours.

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"ACC is an orphan disease with no approved therapies and patients with Notch mutations have a more aggressive disease course and poorer survival outcomes as compared to patients with Notch wild-type. R/M ACC remains a significant area of unmet need, and I am encouraged by the preliminary results that AL101 monotherapy has demonstrated to-date. Coupled with new preclinical data showing that AL101 in combination with approved targeted therapies could potentially treat a greater proportion of ACC tumors, regardless of Notch mutations, it will be exciting to see how AL101 may be developed as a viable treatment option for R/M ACC patients," said Alan L. Ho, M.D., Ph.D., Medical Oncology, Memorial Sloan Kettering Cancer Center and Lead Investigator in The ACCURACY Trial. "While these results are still preliminary, the safety profile of AL101 and the disease control rate of 70% are promising indicators in this incredibly difficult to treat patient population."

"The preliminary safety and efficacy data from the 6mg cohort of our ongoing ACCURACY trial of AL101 highlights a favourable profile. We are pleased to see that AL101’s safety profile continues to be tolerable and manageable, providing us with potential dosing flexibility as we continue to advance our development plans," said Gary Gordon, M.D., Ph.D., Chief Medical Officer of Ayala. "We continue to see strong potential for AL101 to transform the treatment landscape for R/M ACC patients with Notch mutations and we look forward to reporting additional clinical data in 2022."

Preliminary Safety and Efficacy Data from 6mg Cohort of ACCURACY Phase 2 Trial:
Ayala presented new preliminary 6mg data from its ongoing ACCURACY Phase 2 clinical trial evaluating the safety and efficacy of AL101 monotherapy for the treatment of patients with R/M ACC harboring Notch-activating mutations. The Phase 2 ACCURACY clinical trial is an open-label, single-arm, multi-center study to assess the clinical activity of AL101 using radiographic assessments of patients with R/M ACC demonstrating disease progression within 6 months prior to dosing.

As of July 9, 2021, all 42 patients enrolled in the 6mg cohort were treated and evaluable for safety and 33 were evaluable for efficacy.

Efficacy:
All evaluable patients were assessed for efficacy for a best response by investigators using RECIST 1.1 criteria.

Disease control rate (DCR) (defined as partial response and stable disease) was 70% (23/33 patients).
Partial responses (PR) were observed in 3 patients (9%).
Stable disease (SD) was observed in 20 patients (61%).
Progressive disease (PD) was observed in 8 patients (24%).
Two patients were determined to be evaluable per protocol but their scans were not available for analyses.
Study is ongoing with several patients remaining on drug as of the cutoff date.
Safety:
AL101 6mg QW treatment in patients with R/M ACC was well tolerated with manageable side effects consistent with those observed in the 4mg QW cohort with no new adverse events (AEs) specific to the 6mg cohort.

Most common treatment-related (TR) AEs of any grade were diarrhea (76%), fatigue (48%), nausea (41%), hypophosphatemia (29%), vomiting (26%) and decreased appetite (26%).
Treatment-related diarrhea was common and occurred in 32 patients (76%) and most were grades 1 and 2. Treatment-related serious diarrhea occurred in 6 patients (14%).
Serious TRAEs were reported in 31% of patients with treatment-emergent AEs leading to discontinuation in 26% of patients.
Two patients experienced a grade 4 TRAE: one patient experienced a seizure and one patient experienced drug-induced liver injury.
Four treatment-emergent patient deaths occurred (10%), one of which was assessed by the investigator to be treatment related.
Ayala plans to report additional data from the ACCURACY study in 2022.

"Our new preclinical study evaluating the potential of improved efficacy of AL101 in combination with approved targeted therapies represents a promising potential approach for additive or synergistic activity of gamma secretase inhibition when combined with various mechanisms of action," said Roni Mamluk, Ph.D., Chief Executive Officer of Ayala. "We observed stronger tumor growth inhibition in ACC PDX models with Notch pathway genes downregulated regardless of mutational status in the combination arm of the study, as compared to AL101 monotherapy. Based on these results, we believe there is a strong rationale for a combination therapy approach to treating ACC, in addition to other cancer indications in which Notch is dysregulated. We look forward to the further development of AL101 in Notch dysregulated tumors, both as monotherapy and in combination."

Preclinical Results of AL101 Combined with Other Drugs for Dual Targeting of Notch Dysregulated Tumors:
In this preclinical study evaluating the potential of combination therapy of AL101 in PDX models of ACC, Ayala compared the differential gene expression of ACC tumors versus normal matched tissue regardless of Notch activation status. Combination compounds were selected based on determination of the pathways that are implicated with approved oncology therapies, including inhibitors of Bcl2, HDAC, FGFR & CDK4/6. Based on a comparison of AL101 alone, each approved drug alone, and the combination of each drug with AL101, Ayala observed additive or synergistic activity of AL101 combined with agents of various mechanisms of action. AL101 in combination demonstrated significant tumor growth inhibition, including regressions, compared to each drug alone, showing significant benefit with dual targeting of Notch and other dysregulated pathways. Additionally, the study indicated that crosstalk between signaling pathways may increase the efficacy of AL101 in R/M ACC regardless of Notch mutational status. These preclinical results demonstrated a compelling rationale for potential expansion to a larger portion of ACC patients and to additional cancer indications.

About Adenoid Cystic Carcinoma (ACC)

ACC is a rare malignancy of the secretory glands including salivary glands, accounting for about 10% of all salivary gland tumors with an annual incidence of 3,400 in the U.S. There is currently no approved standard of care for patients with recurrent/metastatic ACC. Patients with locoregional disease undergo surgery and radiation therapy, with recurring disease treated by chemotherapy. ACC is an immunologically "cold" tumor that is refractory to chemotherapy, with a recurrence rate of about 60% after initial surgery. The Notch pathway has been determined to be an oncogenic driver of ACC and its dysregulation plays a key role in tumorigenesis and correlates with a distinct pattern of metastasis and a poor prognosis.

About AL101

AL101 is an investigational small molecule Gamma Secretase Inhibitor (GSI) that is designed to potently and selectively inhibit Notch 1, 2, 3 and 4, and is currently being evaluated in two Phase 2 clinical studies, ACCURACY and TENACITY, in patients with adenoid cystic carcinoma (ACC) and in patients with triple negative breast cancer (TNBC), respectively. AL101 is designed to inhibit the expression of Notch gene targets by blocking the final cleavage step by the gamma secretase required for Notch activation. Ayala obtained an exclusive, worldwide license to develop and commercialize AL101 from Bristol-Myers Squibb Company in November 2017. AL101 was granted U.S. FDA Fast Track Designation and Orphan Drug Designation for the treatment of ACC.

On September 16, 2021 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company developing next generation cancer and infectious disease immunotherapies and vaccines, reported a $55.0 million private investment in public equity (PIPE) financing from the sale of 5,000,000 shares of its common stock at a price per share of $11.00 (Press release, Gritstone Oncology, SEP 16, 2021, View Source [SID1234592013]). Gross proceeds from the PIPE financings total $55.0 million, before deducting placement agent fees and offering expenses. The PIPE is being led by Frazier Life Sciences Public Fund, with additional participation from Redmile Group and Gilead Sciences.

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"As long-term backers of Gritstone, we continue to be impressed by the company’s progress and emergence as a leader in development of next generation immunotherapies and vaccines for cancer and infectious diseases," said Jamie Brush, M.D., General Partner and Portfolio Manager of the Frazier Life Sciences Public Fund. "We believe Gritstone’s EDGE platform and integrated vaccine manufacturing capabilities uniquely position the company to rapidly expand into infectious disease vaccine development with a potentially refrigerator stable self-amplifying mRNA vaccine platform. This financing will help ensure Gritstone has the resources to move quickly in this exciting new area, and we are excited to support the company in its next phase of growth."

The closing of the PIPE financing is subject to customary closing conditions and is expected to close by September 17, 2021. Cowen served as the sole placement agent for the PIPE financing.

The securities sold in this private placement have not been registered under the Securities Act of 1933, as amended, and may not be offered or sold in the U.S. except pursuant to an effective registration statement or an applicable exemption from the registration requirements. Gritstone bio has agreed to file a registration statement with the Securities and Exchange Commission registering the resale of the shares of common stock issued in this private placement.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On September 16, 2021 ALX Oncology Holdings Inc., ("ALX Oncology") (Nasdaq: ALXO), a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint pathway, reported the initiation of a Phase 1/2 investigator-sponsored trial of evorpacept (also known as ALX148), a next generation CD47 blocker, in combination with rituximab and lenalidomide for the treatment of patients with indolent and aggressive non-Hodgkin lymphoma ("NHL") (Press release, ALX Oncology, SEP 16, 2021, View Source [SID1234591864]). This study is being led by Dr. Paolo Strati at The University of Texas M.D. Anderson Cancer Center ("MDACC"), one of the largest multidisciplinary programs in the U.S. for treating NHL.

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"We are excited to launch this study that builds upon the promising anti-tumor activity and tolerability observed from ASPEN-01, ALX Oncology’s Phase 1b study to investigate the combination of evorpacept and rituximab in patients with advanced relapsed and refractory NHL," said Paolo Strati, M.D., Assistant Professor, Department of Lymphoma-Myeloma and Department of Translational Molecular Pathology, MDACC. "NHL remains a difficult-to-treat cancer and patients are in desperate need for more therapeutic options to help improve disease outcomes. From a mechanistic perspective, the combination of a CD47 blocker and rituximab, as well as the combination of lenalidomide and rituximab, have demonstrated clinical activity against NHL. As these doublet combinations act through different but synergistic mechanisms, and have non-overlapping individual toxicity profiles, we anticipate the triplet combination of evorpacept, rituximab and lenalidomide will positively impact efficacy without increasing toxicity."

About Non-Hodgkin Lymphoma

Approximately 500,000 people worldwide are diagnosed with NHL each year. In the U.S., NHL is the seventh most common type of cancer, and over 80,000 newly diagnosed cases of NHL are estimated in 2021. Treatment options are currently limited and resistance to existing therapies or relapse following treatment is common. The most prevalent form of NHL, accounting for about 40% of newly diagnosed NHL cases, is an aggressive form called diffuse large B-cell lymphoma ("DLBCL"). Patients with relapsed or refractory DLBCL have an extremely poor prognosis with a median survival of approximately 6 months. Indolent lymphomas comprise another common form of NHL, especially among elderly individuals, where safe and effective chemotherapy-free options for these patients are urgently needed.

On September 16, 2021 CureLab Oncology’s a clinical-stage biotech company, reported at this year’s European Society for Medical Oncology (Press release, CureLab Oncology, SEP 16, 2021, View Source [SID1234587960]). Two reports were accepted and are featured as e-posters in the oncology/PRO educational portal for oncologists.

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The reports describe findings resulting from CureLab’s clinical trials of Elenagen, an experimental DNA therapy, that are currently underway at N.N. Alexandrov National Cancer Centre of Belarus under the direction of a team led by Deputy Director Professor Sergei Krasny, MD, DSc.

The reports are available online:

Plasmid encoding p62/SQSTM1 administered in combination with CMF chemotherapy improves outcomes in metastatic triple-negative breast cancer patients
Adding dosing of plasmid encoding p62/SQSTM1 to gemcitabine chemotherapy may provide clinical benefits to patients with platinum-resistant ovarian cancer

About Elenagen
CureLab’s lead investigational compound is code-named Elenagen, an experimental DNA therapy that consists of a circular piece of DNA called a plasmid that includes a gene for a human protein called p62/SQSTM1. In animal studies and Phase I/II human trials conducted ex-US, Elenagen has shown promise in reversing tumor grade, changing the tumor microenvironment, and enhancing the anti-cancer effects of chemotherapy. Experimental results indicate a mitigation of chronic inflammation and stimulation of an immune response to the tumor.

On September 16, 2021 Carrick Therapeutics, an oncology-focused biopharmaceutical company discovering and developing highly differentiated therapies, reported that encouraging initial clinical data on samuraciclib (CT-7001), an oral and first-in-class inhibitor of CDK7, at the 2021 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (Press release, Carrick Therapeutics, SEP 16, 2021, View Source [SID1234587940]).

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Data presented from a Phase 2a study of samuraciclib in combination with fulvestrant in women with hormone receptor positive (HR+), HER2- advanced breast cancer (BC) previously treated with a CDK4/6 inhibitor (abstract: 1346 (265P)) demonstrated clinical activity and tolerability that supports further clinical development of the combination.

"Today, for the first time, we presented data from a clinical trial of our oral CDK7 inhibitor, samuraciclib. Results of the Phase 2a study in combination with fulvestrant demonstrated clinical activity and tolerability in patients with HR+, HER2- advanced breast cancer, reinforcing our conviction that samuraciclib has potential to be a first and best-in-class treatment," said Tim Pearson, Chief Executive Officer of Carrick Therapeutics. "As a reminder, the FDA recently granted Fast Track designation to samuraciclib in combination with fulvestrant for CDK4/6 inhibitor resistant patients. This patient population is particularly difficult to treat, with a recent trial showing only 8 weeks mPFS benefit when women are treated with fulvestrant alone. Based on this initial data, we believe samuraciclib has the potential to provide a clinically meaningful benefit for all patients, most notably in those women that are TP53 wildtype. In addition to fulvestrant, we are exploring additional samuraciclib combinations, including with giredestrant, a next-generation oral SERD, through our recently announced clinical collaboration with Roche in metastatic breast cancer. We thank the women that participated in this Phase 2a trial and look forward to continuing the fight against this and other types of cancer."

As part of the Phase 2a study of samuraciclib in combination with fulvestrant in patients with advanced HR+, HER2- BC, 31 patients were enrolled with difficult-to-treat disease. 81% of these patients had visceral disease, including 45% with liver metastasis. All patients enrolled previously progressed following treatment with a CDK4/6 inhibitor. Of the 31 patients enrolled in the study, 24 patients were evaluable for response at the time of data cut-off:

17 (71%) had tumour shrinkage, with a best RECIST response of partial response (PR) in two (8%) patients and stable disease (SD) in 13 (54%) patients.
Median progression-free survival (mPFS) of the intent-to-treat (ITT) population was 16.1 weeks (n=31).
Notably, patients with no mutation in the TP53 gene had a mPFS of 32.0 weeks (n=18).
Prolonged disease control was also apparent in patients with no liver metastases at baseline (n=17), with mPFS having not yet been reached. At the point of this data cut-off, mPFS would be at least 28 weeks.
Adverse events were predominantly low-grade gastrointestinal (GI) events that were reversible and manageable using standard prophylactic treatment. No significant neutropenia or myelosuppression associated with other CDK inhibitors were observed.
This data supports the further development of samuraciclib in HR+ advanced BC.
"The data from this study show excellent preliminary evidence of activity of samuraciclib in combination with fulvestrant," said Dr. Sacha Howell, The Christie NHS Foundation Trust, Manchester, UK and a primary investigator in the Phase 2a study. "This population of patients, previously treated with CDK4/6 inhibitors, are known to have previously demonstrated short PFS benefit from fulvestrant alone. The efficacy data, particularly in participants with wildtype TP53, exceeded my expectations and offers the potential for durable endocrine disease control, further delaying the need for chemotherapy. Those participants remained on therapy for prolonged durations demonstrates tolerability and the main GI toxicity was manageable with supportive medication."

"Following the positive initial Phase 2a data, we are preparing to advance the randomized Phase 2b study of HR+, HER2-, post-CDK4/6 inhibitor breast cancer patients," said Dr. Stuart McIntosh, Chief Medical Officer of Carrick Therapeutics. "A key distinction from the Phase 2a will be the inclusion of patients with RECIST non-measurable disease in addition to those with visceral disease in the Phase 2b, in-line with the real-world population. Given the success noticed in the sub-group of patients with no mutation in the TP53 gene population, we will prospectively evaluate and stratify by mutation status as well. This success aligns with the known biological function of TP53 since its activation has been shown to sensitize cancer cells to CDK7 inhibition. Approximately 75% of breast cancer patients are TP53 wild-type, and we believe this may be an important potential biomarker for future studies."

In addition to the Phase 2a data presented today, data from the first-in-human study of samuraciclib in patients with advanced solid malignancies (abstract: 943 (230MO)) will be shared during an oral presentation at ESMO (Free ESMO Whitepaper) from 17:10 BST (12:10pm ET) on September 18, 2021. As part of the study, 44 patients were treated with escalating doses of samuraciclib monotherapy, which demonstrated evidence of antitumor activity with a manageable safety profile.

About Samuraciclib (CT7001)
Samuraciclib is the most advanced oral CDK7 inhibitor in clinical development. Inhibiting CDK7 is a promising therapeutic strategy in cancer as CDK7 regulates the transcription of cancer-causing genes, promotes uncontrolled cell cycle progression and resistance to anti-hormone therapy. Samuraciclib has demonstrated a favorable safety profile and encouraging efficacy in early clinical studies. In addition to the above study, it is currently being evaluated in triple negative breast cancer (TNBC) and prostate cancer with further potential in pancreatic, ovarian and colorectal cancers. Samuraciclib has been granted Fast Track designations from the U.S. Food and Drug Administration (FDA) for use in combination with fulvestrant for the treatment of CDK4/6i resistant HR+, HER2- advanced breast cancer and in combination with chemotherapy for the treatment of locally advanced or metastatic TNBC.