On October 21, 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 first patient has been dosed in the Phase 1/2 ASPEN-05 study evaluating the combination of evorpacept, a next-generation CD47 blocker, with venetoclax and azacitidine for the treatment of patients with acute myeloid leukemia ("AML") (Press release, ALX Oncology, OCT 21, 2021, View Source [SID1234591867]).

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The Phase 1 portion of the ASPEN-05 study will characterize the safety and confirm the dose of evorpacept in combination with venetoclax and azacitidine in patients with relapsed/refractory AML and previously untreated AML who are not candidates for intensive induction therapy. The Phase 2 portion of the study will evaluate the efficacy of the combination in patients with previously untreated AML who are not candidates for intensive induction therapy.

ASPEN-05 is based on promising preclinical data with evorpacept in combination with venetoclax and azacitidine in non-clinical models of leukemia, as well as clinical data from an ongoing phase 1 study (NCT03013218) evaluating evorpacept in combination with multiple anti-cancer agents in both solid and hematologic malignancies.

"Patients with either relapsed/refractory AML or previously untreated AML who are not considered eligible for intensive induction regimens remain in urgent need of tolerable and effective new therapies," said Harry Erba, M.D., Ph.D., Director of the Leukemia Program at the Duke Cancer Institute. "We are looking forward to evaluating the addition of evorpacept to venetoclax and azacitidine. ALX148 was specifically designed for use in combination to maximize phagocytosis of tumor cells while minimizing the toxicities commonly associated with other CD47-targeted approaches."

"ASPEN-05 builds upon compelling evorpacept combination activity observed in non-clinical models of leukemia. With demonstrated tolerability of evorpacept in multi-agent chemotherapy regimens, we are excited to characterize evorpacept with this standard backbone of AML therapy," said Sophia Randolph, M.D., Ph.D., Chief Medical Officer of ALX Oncology. "Through blockade of the CD47 myeloid checkpoint, evorpacept in combination with venetoclax and azacitidine may potentially transform treatment options for patients with AML."

The ASPEN-05 trial is registered under NCT04755244. ALX Oncology owns worldwide commercial rights to evorpacept.

About Acute Myeloid Leukemia

AML is an aggressive blood cell cancer that can rapidly progress and lead to death if not treated promptly. AML is the most common form of acute leukemia in adults, with an estimated 19,940 new cases and 11,180 deaths from AML in the United States. Due to advanced age and comorbidities at the time of diagnosis, a significant number of patients are not considered eligible for intensive and potentially curative therapies. Despite advances in available care, the estimated 5-year survival for patients in the United States with AML remains only 29%.

On October 21, 2021 BeyondSpring (the "Company" or "BeyondSpring") (NASDAQ: BYSI), a global pharmaceutical company focused on the development of cancer therapeutics, reported the first patient has been treated in an investigator-initiated, open-label Phase 2 study with lead asset plinabulin in combination with nivolumab + ipilimumab in patients with 3rd line recurrent small-cell lung cancer (SCLC) who failed checkpoint inhibitors and platinum-based chemotherapy. Plinabulin is a selective immunomodulating microtubule-binding agent (SIMBA), which is a potent antigen presenting cell (APC) inducer (Press release, BeyondSpring Pharmaceuticals, OCT 21, 2021, View Source;utm_medium=rss&utm_campaign=beyondspring-announces-first-patient-treated-in-phase-2-study-with-plinabulin-combined-with-nivolumab-ipilimumab-in-patients-in-3rd-line-recurrent-small-cell-lung-cancer-patients-who-failed-checkpoi [SID1234591682]). This Phase 2 study, to be conducted through the Big Ten Cancer Research Consortium in 7 U.S. clinical centers, comes after the successful completion of the Phase 1 dose escalation study portion of this Phase 1/2 study.

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"For patients with extensive stage SCLC who failed chemo and checkpoint inhibitors, effective treatment options are limited. By exploring this novel immunotherapy combination and expanding on the encouraging Phase 1 data, there is an opportunity to address this unmet medical need," commented Jyoti Malhotra, M.D., M.P.H., Principal Investigator, medical oncologist at Rutgers Cancer Institute of New Jersey. "In the Phase 1 study, the addition of plinabulin to nivolumab + ipilimumab was able to induce tumor responses in patients who failed chemotherapy and checkpoint inhibitors with ORR at 43%, double the ORR of nivolumab + ipilimumab in Checkmate 032. An added bonus is the marked reduction in Grade 3/4 IR-AEs from historical 37% to 12.5%; IR-SAE typically leads to permanent discontinuation of PD-1 and CTLA-4 combination. The ability to both enhance the anti-cancer effects and reduce the Grade 3/4 IR-AEs of PD-1 and CTLA-4 inhibitors makes plinabulin an ideal addition to these checkpoint inhibitors for establishing the concept of a ‘chemo-free’ therapeutic strategy for cancer patients."

In this Phase 2 study, up to 26 patients with histological or cytological confirmed extensive-stage SCLC who progressed after at least one platinum-based chemotherapy regimen and checkpoint inhibitors will receive the triple combination of plinabulin + nivolumab + ipilimumab. Patients in the Phase 2 study will continue treatment until disease progression, development of unacceptable toxicity, or one of the protocol-defined reasons for treatment discontinuation occurs.

Dr. Ramon Mohanlal, BeyondSpring’s Executive VP of R&D and Chief Medical Officer added, "Confirmation of the positive Phase 1 data in Phase 2 will open the doors for adding plinabulin to PD-1 and CTLA-4 inhibitors as a ‘chemo-free’ triple combination therapeutic strategy in the cancer types wherein plinabulin has single agent activity, which include bladder cancer, TNBC, CNS cancers, gastric cancers and sarcoma. We firmly believe that plinabulin’s differentiated immune MOA, as a SIMBA, provides the basis for its potential broad applicability as an anti-cancer agent in multiple cancer indications. The recent success of Dublin-3 showing plinabulin’s durable anti-cancer benefit in long term survivals in NSCLC patients is our first step towards this goal. We’re also very thankful to be working with experts at the Big Ten Research Consortium who realized the potential for plinabulin and chose it to be the subject of this combination therapy clinical trial."

About Plinabulin

Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent (SIMBA), which is a potent antigen presenting cell (APC) inducer. It is a novel, intravenous infused, patent-protected, NDA-stage asset for CIN prevention and a Phase 3 anti-cancer candidate for non-small cell lung cancer (NSCLC) with recently released positive topline data. Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anticancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells, and the second is early-onset of action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs). Plinabulin received Breakthrough Therapy designation from both U.S. and China FDA for the CIN prevention indication. As a "pipeline in a drug," plinabulin is being broadly studied in combination with various immuno-oncology agents that could boost the effects of the PD-1/PD-L1 antibodies and re-sensitize PD-1/PD-L1 antibody-resistant patients.

SCLC Phase 1 IIT Study (Big Ten Consortium)

In the Phase 1 dose escalation study evaluating 20 mg/m2 and 30 mg/m2 doses of plinabulin combined with nivolumab and ipilimumab in 16 patients, the 30 mg/m2 dose was selected for the Phase 2 trial. All 16 patients were evaluated for safety, and 13 patients were evaluated for efficacy.

The combination demonstrated favorable safety and tolerability. There were no Grade 4 events in the 16 patients studied, and 12.5% experienced Grade 3 IR-AEs, compared to 37% Grade 3/4 IR-AEs reported with nivolumab + ipilimumab in SCLC. ORR was 50% for the six patients receiving the triple IO combination as second line therapy after platinum. Three patients had partial responses (PR), with best tumor reduction at target lesions of 100%, 53% and 45%, respectively. ORR was 43% for the seven patients receiving the triple IO combination as third line therapy, who had either failed or had not responded to platinum and PD-1/PD-L1 inhibitors. Three patients had PRs, with best tumor reductions at target lesions of 78%, 75% and 52%, respectively. Duration of therapy for these 3 PR patients was 18 months, five months (still on treatment) and three months, respectively.

On October 21, 2021 Blueprint Medicines Corporation (NASDAQ: BPMC), reported that it will host a live conference call and webcast at 8:30 a.m. ET on Thursday, October 28, 2021 to report its third quarter 2021 financial results and provide a corporate update (Press release, Blueprint Medicines, OCT 21, 2021, View Source [SID1234591705]).

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To access the live conference call, please dial 844-200-6205 (domestic) or 929-526-1599 (international), and refer to conference ID 963004. A webcast of the call will also be available under "Events and Presentations" in the Investors & Media section of the Blueprint Medicines website at View Source The archived webcast will be available on Blueprint Medicines’ website approximately two hours after the conference call and will be available for 30 days following the call.

On October 21, 2021 Johnson & Johnson (NYSE: JNJ) reported that its Board of Directors has declared a cash dividend for the fourth quarter of 2021 of $1.06 per share on the company’s common stock (Press release, Johnson & Johnson, OCT 21, 2021, View Source;johnson-announces-quarterly-dividend-for-fourth-quarter-2021-301406101.html [SID1234591738]). The dividend is payable on December 7, 2021 to shareholders of record at the close of business on November 23, 2021. The ex-dividend date is November 22, 2021.

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On October 21, 2021 Cedilla Therapeutics, a biotechnology company bringing a new dimension to precision oncology, reported its two lead conditional inhibitor programs: an inhibitor of TEAD for the treatment of solid tumors, such as mesothelioma and certain squamous cell carcinomas; and a highly selective inhibitor of CDK2 for the treatment of multiple tumor types, including CDK4/6-resistant breast cancer, ovarian, uterine, stomach, and esophageal cancers (Press release, Cedilla Therapeutics, OCT 21, 2021, View Source [SID1234591683]). Both programs are wholly owned by Cedilla. In addition, Cedilla is pursuing discovery research efforts against a portfolio of high value cancer targets.

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"Over the past three years, we have built an integrated suite of capabilities that enable us to understand the relevant functional states of important yet elusive cancer targets, and identify previously unrecognized small molecule binding sites," said Alexandra Glucksmann, Ph.D., President and Chief Executive Officer of Cedilla Therapeutics. "Today, we are excited to announce our two lead programs from our internal efforts to discover conditional inhibitors: an inhibitor of TEAD and a highly selective inhibitor of CDK2. We look forward to advancing these programs closer to the clinic and creating novel medicines with the potential to deliver profound benefit to patients."

The discovery of both programs was enabled by Cedilla’s novel approach to developing small molecule conditional inhibitors. Cedilla recognizes proteins as dynamic entities, whose function is orchestrated by inter-molecular associations and post-translational tailoring. By accounting for the native full-length protein with relevant post-translational modifications, protein-protein interactions and sub-cellular localization, Cedilla is able to understand proteins in their functional state to discover new ways to access key cancer drivers that have been considered undruggable.

"Since our founding, we have worked to develop a deep understanding of high-value, historically inaccessible targets, and to identify new vulnerabilities that may enable us to drug them more effectively, delivering superior clinical benefit," said Brian Jones, Ph.D., Chief Scientific Officer. "Based on preclinical data, I believe our TEAD and CDK2 programs have clear advantages relative to historical approaches, offering the opportunity for preferential clinical utility, in terms of targeted efficacy or combinability with other therapeutic mechanisms. We look forward to advancing both programs into IND-enabling studies next year."

About Cedilla’s TEAD Program

TEAD (transcriptional enhanced associate domain) is a key component of the Hippo signaling pathway that is aberrantly regulated in solid tumors such as mesothelioma and certain squamous cell carcinomas. TEAD is also increasingly implicated in resistance to targeted therapies, including those for the treatment of EGFR-mutated and KRAS-mutated lung cancer.

Cedilla’s program is designed to inhibit the function of TEAD by preventing a post-translational modification required for full function. The company’s portfolio of TEAD inhibitors encompasses multiple chemotypes with different effects on TEAD isoforms and cofactors, providing Cedilla a range of starting points for selecting a candidate with an optimal profile for effective and combinable TEAD inhibition. Cedilla plans to be conducting investigational new drug (IND) application-enabling studies in the first half of 2022.

About Cedilla’s CDK2 Program

CDK2 (cyclin dependent kinase 2) has been a major target of interest for cancer indications driven by amplification or high levels of Cyclin E, including in roughly half of patients with CDK4/6-resistant breast cancer. In addition, Cyclin E amplification drives genetically defined subsets of ovarian, uterine, stomach and esophageal cancers. The CDK2-Cyclin E cancer node has remained inaccessible due to challenges achieving selectivity over other CDKs (cyclin dependent kinases), particularly CDK1, and Cyclin E isoforms.

Cedilla has developed a unique series of inhibitors that bind to a previously unreported site on the CDK2-Cyclin E complex with unprecedented selectivity, potentially offering a substantial advance over two decades of industry efforts. Preclinical characterization suggests that the exquisite selectivity of Cedilla’s inhibitor could result in a better safety profile compared to traditional kinase inhibitors, particularly with respect to dose-limiting hematological toxicities. Cedilla plans to be conducting IND application-enabling studies in the second half of 2022. In addition, based on its unique insights into Cyclin biology, Cedilla has the potential to pursue additional drug discovery programs against related targets.