On September 16, 2021 Athenex, Inc., (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies for the treatment of cancer and related conditions, reported the presentation of data from a Phase 1 study to assess the safety, tolerability, and activity of oral paclitaxel and encequidar (Oral Paclitaxel) in combination with pembrolizumab in patients with advanced solid malignancies (Press release, Athenex, SEP 16, 2021, View Source [SID1234587797]). The data are being presented in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2021, being held from September 16th to September 21st.

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"The encouraging interim Phase 1 data suggest promising anti-cancer activity and expected safety and tolerability observations for oral paclitaxel with pembrolizumab in lung cancer patients who had progressed on PD1/PDL1 therapies," said Dr. Rudolf Kwan, Chief Medical Officer of Athenex. "PD1/PDL1 therapies are important treatments for lung cancer but most patients eventually progress, and those patients represent an area of high unmet medical need. We are currently working to confirm these data in the dose expansion phase of this study."

Phase 1 Study with Expansion Cohorts to Assess the Safety, Tolerability, and Activity of Oraxol (Oral Paclitaxel + Encequidar) in Combination with Pembrolizumab in Subjects with Advanced Solid Malignancies

The primary objective for the dose escalation phase of the study was to determine the maximum tolerated dose (MTD) and identify the recommended Phase 2 dose (RP2D) of Oral Paclitaxel in combination with pembrolizumab in patients with advanced solid tumors.

The dose escalation phase of the study enrolled 21 patients. Activity data were presented on 17 patients who were evaluable for a response, including eight NSCLC patients as well as patients with head and neck cancer, uveal melanoma, oesophageal cancer, colon cancer and bladder cancer. Four patients had partial response, 10 patients had stable disease, and three patients had progressive disease. The duration on treatment ranged from 9 to 676+ days.

There were a total of 10 NSCLC patients enrolled, of which eight were evaluable for response. Four patients achieved partial response and four patients achieved stable disease. All had discontinued previous checkpoint inhibitor therapy due to progressive disease.

MTD of the combination was not reached. The RP2D in combination with pembrolizumab was selected as Oral Paclitaxel 270 mg QD Days 1-3 for 2 weeks of a 3-week cycle. The study is proceeding to expansion cohorts and will enroll additional patients with NSCLC to further evaluate the safety and clinical activity of Oral Paclitaxel with pembrolizumab.

About the Phase 1 Study of Oral Paclitaxel and Encequidar in Combination with Pembrolizumab

The Phase 1 study is an open-label dose-escalation design study, to be followed by a 2-arm expansion cohort. The dose escalation utilized the "3+3" design and eligible patients had metastatic or unresectable solid tumors for which pembrolizumab is an FDA approved therapy. The Oral Paclitaxel dose range explored was 270-330mg administered for 2 days up to a maximum of 5 days per week x 2 weeks of a 3-week cycle. Pembrolizumab 200mg IV was administered every three weeks. The primary objective for Part A of the study was to determine the maximum tolerated dose (MTD) and identify the recommended Phase 2 dose of Oral Paclitaxel in combination with pembrolizumab in subjects with advanced solid tumors. Secondary objectives included safety and tolerability, the pharmacokinetics of paclitaxel, and preliminary anti-tumor activity. MTD and dose limiting toxicities were determined based on toxicities observed during the first 3-week cycle of treatment. Response was determined by CT scan evaluated by RECIST 1.1 every 9 weeks. The Part B dose expansion phase will enroll subjects with NSCLC to further evaluate the activity, safety and tolerability of the study treatment.

For further information about the study, visit ClinicalTrials.gov, identifier: NCT03588039.

On September 16, 2021 Aileron Therapeutics (Nasdaq: ALRN), a chemoprotection oncology company focused on fundamentally transforming the experience of chemotherapy for cancer patients, reported new clinical data at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2021 supporting ALRN-6924’s best-in-class potential as a chemoprotective agent (Press release, Aileron Therapeutics, SEP 16, 2021, View Source [SID1234587796]). The company presented final results from its completed Phase 1b trial of ALRN-6924 in patients with small cell lung cancer (SCLC) receiving second-line topotecan treatment, which demonstrated ALRN-6924’s ‘triple-play efficacy’ for the reduction of neutropenia, thrombocytopenia and anemia, as well as a reduction of platelet and red blood cell transfusions, as compared to historical controls. Aileron today also presented preliminary results from its ongoing Phase 1 pharmacology study of ALRN-6924, which confirmed 0.3 mg/kg as the optimal dose for ALRN-6924 and confirmed its novel p53 biomarker-driven mechanism of action, as well as its pharmacodynamic effects, including time to onset, magnitude and duration.

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Aileron is developing ALRN-6924 to selectively protect healthy cells in patients with cancers that harbor p53 mutations to reduce or eliminate chemotherapy-induced side effects while preserving chemotherapy’s attack on cancer cells. ALRN-6924, a first-in-class MDM2/MDMX dual inhibitor, is designed to activate p53 in normal cells, which in turn upregulates p21, which pauses cell cycle in normal cells but not in p53-mutated cancer cells.

"We are pleased to present final results from our completed Phase 1b trial of ALRN-6924 in patients with SCLC being treated with topotecan and preliminary results from our ongoing Phase 1 pharmacology study in healthy volunteers. The data presented at ESMO (Free ESMO Whitepaper) further strengthen our belief in ALRN-6924’s best-in-class potential in the emerging chemoprotection space," said Manuel Aivado, M.D., Ph.D., President and CEO of Aileron. "With our precision medicine strategy, our vision is to bring the first selective chemoprotective agent to all patients with p53-mutated cancer while ensuring no interruption of chemotherapy. We believe chemoprotection during chemotherapy, ultimately, should be as compulsory as anesthesia during surgery."

ALRN-6924 Phase 1b SCLC Trial Final Results

Aileron conducted a Phase 1b open-label clinical trial to evaluate ALRN-6924 as a chemoprotective agent against bone marrow-related, chemotherapy-induced toxicities in patients with SCLC undergoing treatment with topotecan. The company reported the final results from this trial in a poster presentation at ESMO (Free ESMO Whitepaper) titled, "A Phase 1b Study of the Dual MDMX/MDM2 Inhibitor, ALRN-6924, for the Prevention of Chemotherapy-induced Myelosuppression" (Abstract/Poster #: 1654P).

A total of 39 patients were enrolled in the trial, 38 of whom were evaluable per the trial protocol. Topotecan (1.5 mg/ m2) was administered on days 1 through 5 of every 21-day treatment cycle. 32 patients (31 evaluable) were treated with ALRN-6924 at 24 hours before each dose of topotecan at the following dose levels: 0.2 mg/kg (N=4), 0.3 mg/kg (N=16), 0.6 mg/kg (N=6; 5 evaluable) and 1.2 mg/kg (N=6). 7 patients were treated with 0.3 mg/kg of ALRN-6924 at 6 hours before each dose of topotecan.

In the Phase 1b SCLC trial, toxicities were evaluated using the National Cancer Institute’s (NCI) Common Terminology Criteria for Adverse Events (CTCAE). Per the trial protocol, patients were not permitted to receive prophylactic G-CSF treatment in cycle 1. The median number of completed topotecan treatment cycles across all cohorts was 3. 13% of patients required topotecan dose reduction. No patients reported NCI CTCAE Grade ≥3 events of nausea, vomiting, diarrhea; 5% had Grade 3 fatigue.

While chemoprotection effects were observed across all ALRN-6924 dose levels studied in the Phase 1b SCLC trial, the 0.3 mg/kg ALRN 6924 dose level given 24 hours prior to topotecan demonstrated the most robust chemoprotection results. None of the patients treated at the 0.3 mg/kg 24 hour ALRN-6924 dose level had a related serious adverse event (SAE). One patient (6%) at the 0.3 mg/kg 24 hour ALRN-6924 dose level required a red blood cell transfusion and a platelet transfusion. In the topotecan plus placebo arm of a recent third-party randomized Phase 2 trial in SCLC patients receiving topotecan (N=28), 41% and 31% of SCLC patients received red blood cell and platelet transfusions, respectively (Hart et al., ASCO (Free ASCO Whitepaper) 2019).

Summary of Final Key Efficacy Findings from ALRN-6924 Phase 1b SCLC Trial

ALRN-6924 (given 24h prior to chemotherapy) Phase 1b Trial
Bone Marrow-Related Key Toxicity Findings
Adverse Events (AEs)* NCI CTCAE ≥ Grade 3

Third Party
Randomized Phase 2
Trial in SCLC
Historical Control‡

Toxicity ALRN-6924
0.3 mg/kg +
Topotecan
N (%)
N=16 ALRN-6924
(All Dose Levels)
Topotecan
N (%)
N=39
Placebo
+ Topotecan
N (%)
N=28
All AEs 14 (88) 35 (90) 27 (96)
Neutropenia 13 (81) 34 (87) 24 (86)
Thrombocytopenia 7 (44) 18 (46) 20 (70)
Anemia 3 (19) 6 (15) 18 (63)
Febrile Neutropenia 0 1 (3) 5 (17) †
Fatigue 1 (6) 2 (5) 2 (7)
Nausea 0 0 1 (4)

Neutropenia
Grade 4 5 (31)** 14 (36)** 21 (76)

*AEs based on laboratory values, as applicable
**For cycle 1
‡ Hart et al. ASCO (Free ASCO Whitepaper) 2019
† Febrile neutropenia assessed in 29 patients

Dr. Vojislav Vukovic, M.D., Ph.D., Chief Medical Officer at Aileron, commented, "The final results from the Phase 1b SCLC we are presenting at ESMO (Free ESMO Whitepaper) are fully consistent with the interim, proof-of-concept data we presented from this trial last year demonstrating ALRN-6924’s ability to protect this very sick patient population against severe and life-threatening bone marrow-related side effects associated with a highly toxic chemotherapy. With the Phase 1b SCLC trial successfully completed, we look forward to continuing our ongoing Phase 1b randomized, double-blind, placebo-controlled trial of ALRN-6924 in patients with advanced non-small cell lung cancer treated with first-line carboplatin plus pemetrexed."

ALRN-6924 Phase 1 Pharmacology Study Initial Results

Aileron is conducting a multi-part Phase 1 pharmacology study in healthy volunteers to evaluate the pharmacokinetics and pharmacodynamics of ALRN-6924. In a poster presentation at ESMO (Free ESMO Whitepaper) titled, "A Phase 1 Study of the Dual MDMX/MDM2 Inhibitor, ALRN 6924, in Healthy Volunteers" (Abstract/Poster #: 1791P), Aileron presented the findings from Parts 1 and 2 of the study. The objectives of these first two parts were to determine a dose of ALRN-6924 that initiated p53-mediated transcriptional regulation and yielded transient cell cycle arrest via p21 induction in human bone marrow while minimizing the signal for apoptosis (Part 1), and to determine the time to onset, magnitude, and duration of bone marrow pharmacodynamic effects (Part 2). The study is ongoing, and Aileron anticipates presenting additional findings at a later date.

Aileron reported results for a total of 37 subjects (females and males aged 18-65) enrolled and evaluated in Parts 1 and 2 of the study. In Part 1, a total of 14 subjects (6 placebo, 4 each at 0.3 and 0.6 mg/kg of ALRN-6924) received one intravenous infusion of ALRN-6924, and bone marrow samples were obtained 8 hours post-infusion. Immunohistochemistry analysis showed that both dose levels yielded robust induction of p21, a p53-regulated mediator of cell cycle arrest, in bone marrow cells, with minimal evidence of apoptosis compared to placebo. In Part 2, 23 subjects allocated to 8 groups received one 0.3 mg/kg infusion of ALRN-6924. Bone marrow samples were obtained at 4, 8, 12, 16, 20, 24, 36, and 48 hours post-infusion. The 0.3 mg/kg dose demonstrated favorable tolerability, with subjects experiencing only mild, transient adverse events. Robust p21 induction was observed in bone marrow cells, with peak expression observed between 4 hours and 16 hours following ALRN-6924 administration.

On September 16, 2021 Medivir AB (Nasdaq Stockholm: MVIR) reported that invites to a conference call on the supporting clinical data from the completed dose escalation section of the phase 1b study with MIV-818, presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) congress (Press release, Medivir, SEP 16, 2021, View Source [SID1234587770]). The conference call will be held today, September 16, at 15:00 CET, to update on the study and the plan for the MIV-818 program.

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Medivir’s lead candidate drug MIV-818 has the potential to become a liver-targeted, orally administered drug that can help patients with liver cancer. In April, it was announced that the overall results from the first part of the phase 1b study with MIV-818 were positive with a good safety and tolerability profile. The results from the completed dose escalation part of the phase 1b study will be presented today as an e-poster (number 527P) at ESMO (Free ESMO Whitepaper). The poster is presented by Dr Debashi’s Sarker, King’s College, London.

The overall safety profile was in line with expectations for this type of drug and patient population. A total of nine evaluable patients with various types of advanced cancer in the liver were enrolled. These were patients that had exhausted approved therapies prior to being enrolled. An important sign of efficacy was that four patients with hepatocellular carcinoma (HCC) showed stable disease in the liver over an extended period of time. Furthermore, liver biopsies from patients demonstrated delivery of MIV-818 to the liver, and a selective effect of MIV-818 on cancer cells across different types of cancer.

– "These positive study results provide further support for Medivir’s development of MIV-818 in HCC. We are now looking forward to explore MIV-818 further in combination with two other mechanism of actions," says Fredrik Öberg, Medivir’s Chief Scientific Officer.

Conference call for investors, analysts and the media

Presenters from Medivir: Magnus Christensen, interim CEO, Tom Morris, CMO and Fredrik Öberg, CSO.

Medivir AB is obliged to make this information public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 08.45 CET on September 16, 2021.

About MIV-818

MIV-818 is a pro-drug designed to selectively treat liver cancers and to minimize side effects. It has the potential to become the first liver-targeted and orally administered drug for patients with HCC and other forms of liver cancer. MIV-818 has completed a phase 1b monotherapy study, and a combination study in HCC is now planned to be initiated during the second half of 2021.

About primary liver cancer

Primary liver cancer is the third leading cause of cancer-related deaths worldwide and hepatocellular carcinoma (HCC) is the most common cancer that arises in the liver. Although existing therapies for advanced HCC can extend the lives of patients, treatment benefits are insufficient and death rates remain high. There are 42,000 patients diagnosed with primary liver cancer per year in the US and current five-year survival is

11 percent. HCC is a heterogeneous disease with diverse etiologies, and lacks defining mutations observed in many other cancers. This has contributed to the lack of success of molecularly targeted agents in HCC. The limited overall benefit, taken together with the poor overall prognosis for patients with intermediate and advanced HCC, results in a large unmet medical need.

On September 15, 2021 ENcell, a contract development and production company specializing in cell therapy, reported on the 15th that it signed a contract manufacturing agreement (CMO) with Ingenium Therapeutics on the 8th for an incurable leukemia treatment (IGNK001) (Press release, Ingenium Therapeutics, SEP 15, 2021, View Source [SID1234643519]).

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With this consignment production contract, ENcell will carry out turnkey production of 1/2 phase of samples and investigational drugs (IP) required for clinical trial approval (IND) of an anti-leukemia targeted NK cell therapy based on the Memory-like NK platform.

Jong-wook Jang, CEO of ENCell, said, "We will do our best to ensure that Ingenium Therapeutics’ NK cell therapy product successfully enters clinical trials," and added, "We will implement Ingenium Therapeutics’ latest technology with our GMP technology and know-how." "It will contribute to the development of advanced biopharmaceuticals," he said.

On September 15, 2021 Celularity Inc. (Nasdaq: CELU), a clinical-stage biotechnology company developing off-the-shelf placental-derived allogeneic therapies, reported the appointment of Andrew L. Pecora, M.D., F.A.C.P., C.P.E., as President effective today (Press release, Celularity, SEP 15, 2021, View Source [SID1234591817]). Reporting to Robert J. Hariri, M.D., Ph.D., Chairperson and Chief Executive Officer, Dr. Pecora will provide senior leadership to advance Celularity’s clinical pipeline toward U.S. Food and Drug Administration (FDA) approval, including responsibility for preclinical and clinical development and regulatory affairs.

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"It is with great pleasure that we announce Andrew’s appointment as Celularity’s President," said Dr. Hariri. "Building on our recent Nasdaq listing, Andrew’s proven track record as an executive leader in biotechnology and healthcare innovation, delivery and reimbursement will help take Celularity to the next level as we advance our clinical pipeline of next-generation placental-derived cellular therapeutic candidates. Andrew and I trained together at the Weill Cornell Medical Center and have worked in cellular medicines on parallel paths for over 30 years," Dr. Hariri continued.

Dr. Pecora commented, "I am excited to take on this new role at Celularity. I have been very impressed by the early clinical insights and underlying translational science of these novel, placental-derived, off-the-shelf cellular medicines. The potential of Celularity’s clinical pipeline, including its CYNK-101, CyCART-19 and APPL-001 programs, is tremendous. I look forward to providing leadership and strategic vision, working with Bob and his team to realize the potential of these novel allogeneic cell therapies for patients with cancer, infectious disease and degenerative disease."

Dr. Pecora is an award-winning clinician, scientist, and healthcare executive and innovator, with a track record of success leading biotechnology companies to pioneer novel cellular medicines. He is among the world’s foremost experts in blood and bone marrow stem cell transplantation, drug development, and the advancement of novel cell therapies. Dr. Pecora previously served as President of the Physician Enterprise, Chief Innovations Officer, and the Institutional Research Official of Hackensack Meridian Health. There, he oversaw more than 7,500 physicians as well as the business and clinical operations of the John Theurer Cancer Center and clinical and basic research of the Center for Discovery and Innovation. Dr. Pecora also is a Professor of Medicine and Oncology at Georgetown University.

Dr. Pecora is Founder and serves as Chairman of Cota, Inc., a real-world evidence-based data and analytics company focused on leveraging information technology and big data analytics to bridge the gap between precision medicine and population-based health outcomes and to accelerate the development of innovative medicines for patients with difficult to treat diseases.

Prior to Cota, Dr. Pecora served as Co-Founder, Chair and CEO of Progenitor Cell Therapy (PCT), an internationally recognized cellular medicine cGMP manufacturing company. He facilitated the purchase of the Dendreon, Inc., which ultimately led to the FDA approval of PROVENGE (sipuleucel-T), the first FDA approved cell therapy used to treat certain men with advanced prostate cancer. Dr. Pecora eventually led the sale of PCT to Caladrius Biosciences, and co-led multiple public and private capital raises that exceeded USD 500 million.

Earlier in his career, Dr. Pecora was Founder and Chairman of Amorcyte, Inc., a clinical-stage cell therapy company focused on developing novel treatments for cardiovascular disease. At Amorcyte, Dr. Pecora led the capital raise, preclinical and clinical development efforts for AMR-001, a cellular therapy product candidate for vascular injury, through Phase 1 development. This work led to Amorcyte’s sale to Caladrius Biosciences, where Dr. Pecora led the regulatory and clinical development efforts for Amorcyte through Phase 2 development and facilitated a Phase 3 registration trial in Japan.

Dr. Pecora has authored more than 200 peer-reviewed publications and holds over 50 patents, many involving cellular medicines. He has led numerous clinical trials in cancer and other diseases serving as principal investigator. He also has served on national and international steering committees, and contributed to international guidelines for development of cellular medicines, FDA regulatory approval and commercialization standards, including FACT-ISCT International Standards for Hematopoietic Cellular Therapy Production, Processing and Administration. An award-winning healthcare executive, he was recognized in 2019 by Modern Healthcare as one of the top 50 influential clinical healthcare executives.