On August 5, 2021 Aprea Therapeutics, Inc. (Nasdaq: APRE), a biopharmaceutical company focused on developing and commercializing novel cancer therapeutics that reactivate mutant tumor suppressor protein, p53, reported that the U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on its clinical trials of eprenetapopt in combination with azacitidine in its myeloid malignancy programs (Press release, Aprea, AUG 5, 2021, View Source [SID1234594084]). The partial clinical hold does not apply to the Company’s ongoing clinical trials in lymphoid malignancies and solid tumors, or the APR-548 clinical trial.

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There are approximately 20 patients currently receiving eprenetapopt in combination with azacitidine in the Company’s myeloid malignancy programs, which includes the MDS, AML and post-transplant maintenance trials, all of which have completed enrollment. Patients who are benefiting from treatment can continue to receive study treatment. As part of the clinical hold, no additional patients can be enrolled to these trials until the partial clinical hold is resolved. Aprea intends to work closely with the FDA to analyze the data, address the specific questions raised, and seek to resolve the partial clinical hold as soon as possible.

"Patient safety is our highest priority," said Christian S. Schade, Chairman and Chief Executive Officer of Aprea. "Based on the totality of the data we have for eprenetapopt, we believe that it continues to be a promising therapeutic option for cancer patients. We are working closely with the FDA to review the data specific to eprenetapopt with azacitidine in our myeloid malignancy trials and will provide an update when we have additional information."

The Company will host a webcast conference call to discuss this announcement on August 6, 2021 at 8:30 AM (ET). Connection details are provided below and are also available on the Events page of Aprea’s website.

On August 5, 2021 Aravive, Inc. (Nasdaq: ARAV), a clinical-stage oncology company developing innovative therapeutics to treat life-threatening diseases, reported recent corporate updates and financial results for the second quarter ended June 30, 2021 (Press release, Aravive, AUG 5, 2021, View Source [SID1234594061]).

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"Aravive continued to make strong progress in advancing the development of AVB-500 in the second quarter of 2021," said Gail McIntyre, Ph.D., DABT, Chief Executive Officer of Aravive. "We are very encouraged by the positive preliminary pharmacokinetic/pharmacodynamic results from the patients dosed at 15 mg/kg in the first portion of the Phase 1b trial of AVB-500 in clear cell renal cell carcinoma, and we plan to initiate the Phase 2 trial in the second half of 2021. Additionally, we are on track to initiate the Phase 1b/2 trial evaluating AVB-500 as a first-line treatment for pancreatic adenocarcinoma, another area of high, unmet medical need, in the second half of 2021."

Recent Corporate Highlights

AVB-500 in Platinum Resistant Ovarian Cancer (PROC): In April 2021, Aravive announced that the first patient was dosed in its registrational Phase 3 trial of AVB-500 in PROC. The global, randomized, double-blind, placebo-controlled adaptive trial is designed to evaluate efficacy and safety of AVB-500 at a dose of 15 mg/kg in combination with paclitaxel versus paclitaxel alone. The Company expects to conduct the interim analysis in the first quarter of 2022.
AVB-500 in Clear Cell Renal Cell Carcinoma (ccRCC): In June 2021, Aravive announced positive initial safety, pharmacokinetic and pharmacodynamic results from the Phase 1b portion of its Phase 1b/2 trial in patients dosed with 15 mg/kg of AVB-500 in combination with cabozantinib who have ccRCC (advanced stage kidney cancer). The data in three evaluable patients showed that AVB-500 was well tolerated with no adverse findings. Based on the pharmacokinetics, pharmacodynamics, and safety data at 15 mg/kg of AVB-500, and approval by the Data and Safety Monitoring Board (DSMB), the Company has expanded the dosing of 15 mg/kg of AVB-500 to at least three additional patients to determine the potential of initiating the Phase 2 portion with this dose. The Company will also continue to investigate higher doses of AVB-500 in the Phase 1b trial to obtain additional safety, pharmacokinetics, and pharmacodynamics information. Aravive expects to complete enrollment in the Phase 1b portion of the Phase 1b/2 trial and initiate the Phase 2 trial in the second half of 2021.
Achieved One Development Milestone with 3D Medicines in Q2 and One Milestone in July 2021 Totaling $9 million in Milestone Payments: In July 2021, Aravive achieved a $3.0 million development milestone based on the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) approval of the Investigational New Drug (IND) application submitted by 3D Medicines Inc. to participate in Aravive’s international AVB-500 Phase 3 PROC clinical trial. The Company also received a $6.0 million milestone payment in June 2021 related to the first patient dosed by Aravive in the AVB-500 Phase 3 registrational clinical trial for PROC in the United States. Under the terms of the collaboration and license agreement with 3D Medicines, Aravive is eligible to receive up to an aggregate of $207 million in development and commercial milestone payments and royalties, including the $9 million already achieved.
Expanded and Strengthened Board of Directors: Aravive appointed three highly experienced biopharmaceutical industry executives, John A. Hohneker, M.D., Sigurd C. Kirk, and Peter T.C. Ho, M.D., Ph.D., to its Board of Directors. Dr. Hohneker serves on the Compensation Committee of the Board, and Mr. Kirk serves on the Audit Committee.
Second Quarter 2021 Financial Results
Revenue for the three and six months ended June 30, 2021 were $3.8 million and $4.0 million, respectively, compared to $0 for both periods in 2020. Revenue for the three and six months ended June 30, 2021 was derived solely from the Company’s collaboration and license agreement with 3D Medicines, and represents a portion of initial signing and milestone payments received from 3D Medicines that is recognized at the time of the receipt and a portion of the payments that is deferred and recognized over the PROC trial period.

Total operating expenses for the three and six months ended June 30, 2021 were $11.2 million and $19.5 million, respectively, compared to $5.7 million and $16.0 million for the same periods in 2020.

Total operating expenses for the three and six months ended June 30, 2021 included non-cash stock-based compensation expense of $0.5 million and $1.0 million, respectively, compared to $0.5 million and $1.2 million for the same periods in 2020. In addition, during the six months ended June 30, 2020, there were non-recurring non-cash charges for impairment of the Company’s right-of-use asset and leasehold improvements of $2.9 million.

For the three and six months ended June 30, 2021, Aravive reported a net loss of $7.1 million and $15.1 million, or $0.35 per share and $0.78 per share, respectively, compared to a net loss of $5.0 million and $15.8 million, or $0.32 per share and $1.02 per share, for the same periods in 2020.

Cash Position
As of June 30, 2021, cash and cash equivalents were $75.4 million, compared to $60.5 million as of December 31, 2020. The Company expects that its current cash and cash equivalents will be sufficient to fund its operating plans into the second half of 2022.

About AVB-500
AVB-500 is a therapeutic recombinant fusion protein that has been shown to neutralize GAS6 activity by binding to GAS6 with very high affinity in preclinical models. In doing so, AVB-500 selectively inhibits the GAS6-AXL signaling pathway, which is upregulated in multiple cancer types including ovarian cancer. In preclinical studies, GAS6-AXL inhibition has shown anti-tumor activity in combination with a variety of anticancer therapies, including radiation therapy, immuno-oncology agents, and chemotherapeutic drugs that affect DNA replication and repair. Increased expression of AXL and GAS6 in tumors has been correlated with poor prognosis and decreased survival and has been implicated in therapeutic resistance to conventional chemotherapeutics and targeted therapies. AVB-500 is currently being evaluated in clinical trials and has been granted Fast Track Designation by the U.S. Food and Drug Administration in platinum resistant recurrent ovarian cancer. Analysis of all safety data to date showed that AVB-500 has been generally well tolerated with no dose-limiting toxicities or unexpected safety signals.

About the AVB-500 Phase 3 PROC Trial
The global, randomized, double-blind, placebo-controlled adaptive trial (GOG-3059/ENGOT OV-66) is designed to evaluate efficacy and safety of AVB-500 at a dose of 15 mg/kg in combination with paclitaxel. The trial is expected to enroll approximately 300-400 patients with high-grade serous ovarian cancer who have received one to four prior lines of therapy at approximately 165 sites in North America, Europe, and Asia. The primary endpoint for the trial is progression-free survival and the secondary endpoint is overall survival. Exploratory endpoints include objective response rate, duration of response, quality of life, clinical benefit rate, pharmacokinetic and pharmacodynamic profile, and AXL/GAS6 ratio. A prospectively defined interim analysis will determine whether randomization will continue with all patients, regardless of prior bevacizumab treatment, or only with patients medically ineligible to receive bevacizumab or who choose not to receive bevacizumab. This trial is being conducted in partnership with The GOG Foundation, Inc. (GOG-F), through the GOG Partners program in the USA, and in partnership with the European Network for Gynecological Oncological Trial (ENGOT) groups in Europe. The Phase 3 trial is listed on clinicaltrials.gov NCT04729608.

About the AVB-500 Phase 1b/2 ccRCC Trial
Aravive initiated its Phase 1b portion of the Phase 1b/2 trial of AVB-500 in ccRCC in March 2021. The Phase 1b portion of the clinical trial, a dose escalation study, is expected to enroll approximately 18 patients in three dosing arms (15 mg/kg, 20 mg/kg and 25 mg/kg) to evaluate tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of AVB-500 in combination with cabozantinib. The controlled, randomized, open-label Phase 2 portion of the clinical trial is expected to enroll approximately 45 patients and investigate the recommended AVB-500 dose identified during the Phase 1b portion of the clinical trial in combination with cabozantinib versus cabozantinib alone. The primary endpoint is progression-free survival. The trial will enroll patients with advanced ccRCC who have progressed on front-line treatment. The Phase 1b/2 trial is listed on clinicaltrials.gov NCT04300140.

On August 5, 2021 Aligos Therapeutics, Inc. (Nasdaq: ALGS), a clinical stage biopharmaceutical company focused on developing novel therapeutics to address unmet medical needs in viral and liver diseases, reported recent business progress and financial results for the second quarter, June 30, 2021 (Press release, Aligos Therapeutics, AUG 5, 2021, View Source [SID1234591815]).

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"Over the past few months, in addition to completing our recent financing, we have made significant strides in advancing our CHB and NASH drug candidates," commented Lawrence Blatt, PhD, MBA, Chairman and CEO of Aligos. "At recent scientific conferences, healthy volunteer data from our STOPS program and initial antiviral data in CHB subjects from our CAM program, were presented. For both the STOPS and CAM programs, enrollment in the first CHB cohort is complete and is ongoing in the second cohort. Additionally, we recently filed the first clinical trial application (CTA) for our ASO drug candidate, ALG-020572, which is anticipated to begin dosing in healthy volunteers in Q4 2021. We are also on track to file a CTA in Q3 for ALG-055009, our NASH drug candidate, and start dosing in healthy volunteers in Q4 2021. We look forward to continuing to advance these important development programs."

Recent Business Progress

Aligos Portfolio of Drug Candidates:

Preliminary safety and pharmacokinetic data in healthy volunteers (HVs) from the ongoing Phase 1a/b multi-part dose range finding trial (NCT04485663) of our S-antigen Transport-inhibiting Oligonucleotide Polymers (STOPS) compound, ALG-010133, were presented at the European Association for the Study of the Liver (EASL) Digital International Liver Congress 2021 (ILC 2021) in June. These data showed that single and multiple doses up to 200 mg and 180 mg, respectively, were generally well tolerated.

Enrollment and dosing in our Phase 1b trial evaluating subjects with CHB is ongoing and we continue to initiate more clinical trial centers to support this study. However, recent delays to enrollment of chronic hepatitis B subjects have been encountered due to COVID-19 related logistical challenges and an increasing number of competitive phase 2 clinical trials. Consequently, data from the planned 3 cohorts, evaluating a range of doses, are expected to be available in the first half of 2022.

Given that STOPS molecules work by a novel mechanism and patient antiviral response characteristics are unknown, we believe it is important to generate a dataset from multiple cohorts. This should enable us to refine the PK-PD model to optimize dosing for evaluation in subsequent cohorts and studies. We plan to unblind virological data, including HBsAg, once dosing in the first three cohorts has been completed.

In addition, evaluation of ALG-000184, a small molecule class II capsid assembly modulator (CAM), was initiated in patients with CHB in April. This dose range finding study (NCT04536337) is evaluating 28 days of once daily oral dosing of ALG-000184 or placebo in treatment naïve/currently not treated CHB patients. Initial 14-day data from the first cohort demonstrated that a 100 mg dose was well tolerated and resulted in significant antiviral activity. These 14-day data were presented at the HBV-TAG 2021 meeting in June. Data from additional cohorts are expected to be presented at one or more scientific conferences in the second half of 2021.

The initial CTA for our third CHB drug candidate, ALG-020572, an antisense oligonucleotide (ASO), was recently filed. We expect to begin evaluating ALG-020572 in HVs in the fourth quarter of 2021.

The CTA for our first nonalcoholic steatohepatitis (NASH) drug candidate, ALG-055009, a thyroid hormone receptor beta agonist, remains on track to be filed in the third quarter of 2021 to enable evaluation in HVs to commence in the fourth quarter of 2021.

Aligos has a broad CHB portfolio that targets different clinically validated mechanisms of action in the hepatitis B virus life cycle. The portfolio includes ALG-000184, a class II CAM, ALG-010133, a STOPS molecule, ALG-020572, an ASO, and ALG-020755, a small interfering RNA (siRNA) drug candidate. The properties of these candidates indicate that their use in combination could yield potentially best-in-class treatment regimens that may achieve higher rates of functional cure than current standard of care. For each of these drug candidates, Aligos plans to initially establish proof of concept as monotherapy in Phase 1 dose range finding trials before evaluating them in combination in subsequent trials.

Corporate:

The company announced the pricing of its underwritten public offering of 4,400,000 shares of common stock at a public offering price of $19.00 per share. In addition, the company granted the underwriters a 30-day option to purchase up to an additional 660,000 shares of common stock at the same terms and conditions. All of the shares of common stock were offered by the company.

The gross proceeds from the offering, before deducting underwriting discounts and commissions and other offering expenses payable by Aligos, were $83.6 million, excluding any exercise of the underwriters’ option to purchase additional shares. The offering closed on July 6, 2021, subject to customary closing conditions.

Financial Results for the Second Quarter 2021

Net losses for the three months ended June 30, 2021 were $29.8 million or basic and diluted net loss per common share of $(0.79) compared to net losses of $20.8 million or basic and diluted net loss per common share of $(7.40) for the three months ended June 30, 2020.

Research and development (R&D) expenses for the three months ended June 30, 2021, were $24.6 million compared with $17.2 million for the same period of 2020. The increase in R&D expenses for this comparative period is primarily attributable to increased expenses related to the Company’s continued development of ALG-010133 and ALG-000184 clinical trial activities, as well as increases in salaries and employee-related expenses and preclinical programs. Total R&D stock-based compensation expense incurred for the three months ended June 30, 2021, was $2.0 million compared with $0.2 million for the same period for 2020.

General and administrative (G&A) expenses for the three months ended June 30, 2021, were $6.6 million compared with $4.1 million for the same periods of 2020. The increase in G&A expenses for this comparative period is primarily attributable to higher employee-related costs associated with the growth of the Company’s operations and additional professional and consulting services related to being a public company. Total G&A stock-based compensation expense incurred for the three months ended June 30, 2021, was $1.5 million compared with $0.1 million for the same period for 2020.

Cash, cash equivalents and short-term investments totaled $190.7 million as of June 30, 2021 compared with $243.5 million as of December 31, 2020.

On August 5, 2021 Imugene Ltd ("Imugene") (ASX: IMU), a clinical stage immuno-oncology company and Celularity Inc. ("Celularity") (Nasdaq: CELU), a clinical-stage biotechnology company developing off-the-shelf placental-derived allogeneic therapies, reported they have entered into a research collaboration in 2021 (Press release, Celularity, AUG 5, 2021, View Source [SID1234591814]). As part of the partnership, Imugene and Celularity will initially collaborate to develop the combination of Imugene’s CD19 oncolytic virus technology and Celularity’s CD19 targeting allogeneic chimeric antigen receptor (CAR) T cellular therapy, CYCART-19, for the treatment of solid tumors. CYCART-19 is a placental-derived T-cell therapy engineered with a CAR that is cryopreserved, allogeneic and available off-the-shelf to clinicians.

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Imugene exclusively licensed the CD19 oncolytic virus technology from City of Hope, a world-renowned independent cancer research and treatment center near Los Angeles. Imugene’s novel strategy to treat solid tumors uses an oncolytic virus to prime the tumor cells for destruction by eliciting the expression of a validated tumor marker, CD19, that can then be used as a target for CAR T cellular therapy.

"We believe the synergy between Celularity’s placental derived cells and our OnCARlytic platform has the potential to shift the cellular medicine paradigm," said Leslie Chong, Managing Director & Chief Executive Officer of Imugene. "In preclinical studies Celularity’s cellular therapies have shown the ability to overcome limitations that have hindered other approaches, including increased proliferation and persistence in vivo, resistance to T-cell exhaustion and low immunogenicity, which allows for repeated dosing. These unique characteristics perfectly align with our vision for a combination treatment strategy, and we look forward to closely working together to bring this treatment strategy to the clinic and patients in need."

Robert J. Hariri, M.D., Ph.D., founder, Chairperson and Chief Executive Officer of Celularity, said, "We are excited to initiate this research collaboration, which we believe will lay the foundation for a new approach to the treatment of solid tumors. Most solid tumors have variable targetable antigens, limiting CAR T-cell therapy efficacy. This treatment strategy with Imugene has the potential to apply to a new range of indications by enabling CD 19 targeted cellular medicine to expand from its current effective usage in CD19 positive lymphomas and leukemia and potentially become applicable to a variety of solid tumors through inducing uniform expression of CD19 in solid tumors.

On August 5, 2021 Apexigen, Inc., a clinical-stage biopharmaceutical company focused on discovering and developing a new generation of antibody therapeutics for oncology, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to sotigalimab (APX005M) for the treatment of soft tissue sarcoma (Press release, Apexigen, AUG 5, 2021, View Source [SID1234590987]). Sotigalimab, Apexigen’s lead therapeutic candidate, is a potentially first-in-class and best-in-class CD40 agonist, with unique epitope specificity and Fc receptor engagement for optimal therapeutic effect and tolerability. In an ongoing Phase 2 clinical trial, sotigalimab is being evaluated in advanced soft tissue sarcoma in combination with doxorubicin, a chemotherapy that is currently considered standard-of-care treatment.

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"We are very pleased to receive Orphan Drug Designation for sotigalimab, an important step toward addressing the medical need that exists for patients with sarcoma," said Xiaodong Yang, M.D., Ph.D., President and Chief Executive Officer. "There are currently limited treatment options available for patients with soft tissue sarcoma, so we are excited by the emerging data from our ongoing Phase 2 study in this indication, coupled with data across our broad clinical development program, that suggest sotigalimab may provide a superior clinical benefit. We will continue to advance our development plans to overcome outstanding challenges in oncology and work with the FDA to bring sotigalimab to patients as efficiently as possible."

The FDA’s Office of Orphan Drug Products grants orphan status to support the development of medicines for underserved patient populations, or rare disorders, that affect fewer than 200,000 people in the United States. Orphan drug designation qualifies the sponsor for various development incentives, including tax credits for qualified clinical testing, up to seven years of marketing exclusivity for the orphan indication and waiver of certain FDA fees.

Apexigen has also received FDA Orphan Drug Designation for sotigalimab for the treatment of esophageal and gastroesophageal junction cancer and for the treatment of pancreatic cancer.

About Sotigalimab (APX005M)
Sotigalimab is a novel, humanized monoclonal antibody that stimulates the anti-tumor immune response. Sotigalimab targets CD40, a co-stimulatory receptor that is essential for activating both innate and adaptive immune systems. Binding of sotigalimab to CD40 on antigen presenting cells (i.e., dendritic cells, monocytes and B-cells) initiates a multi-faceted immune response bringing multiple components of the immune system (e.g., T cells, macrophages) to work in concert against cancer. Sotigalimab is currently in& Phase 2 clinical development for the treatment of cancers such as esophageal and gastroesophageal junction cancers, melanoma, rectal cancer and sarcoma in various combinations with immunotherapy, chemotherapy, radiation therapy or a cancer vaccine. Additional information on clinical trials for sotigalimab can be found at www.clinicaltrials.gov.