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Ascentage Pharma Announces Publication of Preclinical Data in Nature Immunology Showing Enhanced T-Cell-Mediated Antitumor Immunity Induced by Its MDM2-p53 Inhibitor APG-115

On March 25, 2021 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported the peer-reviewed publication of preclinical data of the company’s investigational novel MDM2-p53 inhibitor APG-115 in the journal Nature Immunology unveiling the role of mouse double minute 2 homolog (MDM2) in CD8⁺ T-cell- mediated immunity (Press release, Ascentage Pharma, MAR 25, 2021, View Source [SID1234577179]).

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Titled "The ubiquitin ligase MDM2 sustains STAT5 stability to control T-cell mediated antitumor immunity," the report is published in today’s Nature Immunology. Shaomeng Wang, PhD, cofounder of Ascentage Pharma, Chairman of the company’s Scientific Advisory Board, and the Warner-Lambert/Parke-Davis Professor of Internal Medicine, Pharmacology, and Medicinal Chemistry at the University of Michigan School of Medicine is a co-author of this study. Weiping Zou, MD, PhD, Charles B. de Nancrede Professor of Pathology, Surgery, Immunology and Biology, and Director, Center of Excellence for Cancer Immunology and Immunotherapy at the University of Michigan is the senior and corresponding author of the study.

The MDM2-p53 complex has a proven role in the development and progression of cancer, opening a potential avenue for therapeutic approaches seeking to disrupt the interaction and increase p53-mediated tumor cell death (apoptosis). However, a major challenge is that there are as yet no approved therapies targeting MDM2-p53.

"Before our study, it was unclear whether the MDM2-p53 axis affects CD8⁺ (cytotoxic or cancer-killing) T-cell-mediated antitumor immunity," said Dr. Wang. "Through a series of biochemical, genetic, and functional studies, we have demonstrated that MDM2 plays a pivotal biological role in T-cell stability, survival, and antitumor immunity, potentially laying a foundation for synergistic effects between MDM2-targeted agents such as APG-115 and cancer immunotherapy."

Using in vivo and other experimental models, the authors demonstrated that mice lacking MDM2 in T cells exhibit more rapidly growing tumors with diminished numbers of tumor-infiltrating CD8⁺ T-cells. The authors also showed that MDM2 stabilizes signal transducer and activator of transcription 5 (STAT5), a protein essential for T-cell function and survival. This is an important finding, in part because Ascentage’s drug candidate APG-115 disrupts the MDM2-p53 complex, potentially acting as an "MDM2 enhancer" to stabilize STAT5 and hence augment T-cell immunity.

APG-115 is a novel, orally active molecule that activates p53-mediated apoptosis in tumor cells with wild-type p53 and/or MDM2 amplification. APG-115 is the first MDM2-p53 inhibitor entering clinical development in China, and is currently being investigated in multiple Phase Ib/II clinical studies in solid tumors and hematologic malignancies in China and the US.

"This is truly uncharted territory," said Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma. "There is a significant unmet clinical need for targeted therapies that disrupt the MDM2-p53 complex and not only eradicate tumor cells but also enhance T-cell-mediated immunity. This publication will bring about the incentives and support that will enable us to further accelerate global development and commercialization of this drug candidate," he said. "Given the promising safety and efficacy data obtained thus far, we will expedite development and are hopeful that APG-115 will soon benefit patients worldwide."

Now underway is a phase 2 clinical trial of APG-115 together with the immune checkpoint inhibitor pembrolizumab in patients with PD-1-inhibitor-refractory or relapsed cancers. These include solid tumor, liposarcoma, urothelial carcinoma, and malignant peripheral nerve sheath tumor, which affects the connective tissues surrounding nerves.

Ikena Oncology Announces Pricing of Initial Public Offering

On March 25, 2021 Ikena Oncology, Inc. ("Ikena"), a targeted oncology company focused on developing cancer therapies targeting key signaling pathways that drive the formation and spread of cancer, reported the pricing of its initial public offering of 7,812,500 shares of common stock at a public offering price of $16.00 per share (Press release, Ikena Oncology, MAR 25, 2021, View Source [SID1234577177]). The shares are expected to begin trading on the Nasdaq Global Market on March 26, 2021 under the ticker symbol "IKNA." The gross proceeds of the offering, before deducting underwriting discounts and commissions and other offering expenses payable by Ikena, are expected to be $125.0 million. The offering is expected to close on March 30, 2021, subject to the satisfaction of customary closing conditions. In addition, Ikena has granted the underwriters a 30-day option to purchase up to an additional 1,171,875 shares of common stock at the initial public offering price.

Jefferies, Cowen, Credit Suisse and William Blair are acting as joint book-running managers for the offering.

The registration statement relating to these securities became effective on March 25, 2021. The offering will be made only by means of a prospectus, copies of which may be obtained from Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by telephone at (877) 821-7388, or by email at [email protected]; Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attn: Prospectus Department, by telephone at (833) 297-2926, or by email at [email protected]; Credit Suisse Securities (USA) LLC, Attention: Prospectus Department, 6933 Louis Stephens Drive, Morrisville, NC 27560, by telephone at (800) 221-1037, or by email at [email protected]; or William Blair & Company, L.L.C., Attention: Prospectus Department, 150 North Riverside Plaza, Chicago, IL 60606, by telephone at (800) 621-0687, or by email at [email protected].

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

Immunome Reports Fourth Quarter and Full Year 2020 Financial Results, Provides Corporate Update

On March 25, 2021 Immunome, Inc. (Nasdaq: IMNM), a biopharmaceutical company that utilizes its human memory B cell discovery engine platform to discover and develop first-in-class antibody therapeutics, reported financial results for the fourth quarter and full year ended December 31, 2020 and provided a corporate update (Press release, Immunome, MAR 25, 2021, View Source [SID1234577176]).

"The fourth quarter of 2020 was a transformational period for Immunome thanks to our successful initial public offering on the NASDAQ exchange, which raised $44.9 million in gross proceeds," said Purnanand Sarma, Ph.D., President and CEO of Immunome. "That positive momentum continued into 2021, with our recent announcements covering the isolation of antibodies capable of neutralizing SARS-CoV-2 variants in pseudovirus testing as part of our IMM-BCP-01 program, and the advancement of IMM-ONC-01, our proprietary antibody against IL-38 for the potential treatment of solid tumors including malignancies of high unmet need such as cancers of the head and neck and the lung, into IND-enabling studies."

Dr. Sarma continued: "Looking ahead, we expect to provide development program updates in the second quarter of 2021 and to file INDs for both IMM-BCP-01 and IMM-ONC-01 in 2021. We remain excited about the prospects for both of our current development programs and reiterate the confidence we have in our discovery engine to move one to two new candidates into IND-enabling studies per year. I very much look forward to updating you on our progress in the months ahead."

Financial Highlights

Cash and cash equivalents: As of December 31, 2020, cash and cash equivalents totaled $39.8 million.
Research and development (R&D) expenses: R&D expenses for the three months ended December 31, 2020 were $1.8 million. R&D expenses for the year ended December 31, 2020 were $7.5 million.
General and administrative (G&A) expenses: G&A expenses for the three months ended December 31, 2020 were $2.2 million. G&A expenses were $4.8 million for the year ended December 31, 2020.
Net loss: Net loss attributable to common stockholders was $4.1 million, or $0.40 per share, for the three months ended December 31, 2020. Net loss attributable to common stockholders was $17.8 million, or $5.26 per share, for the year ended December 31, 2020.
As of December 31, 2020, Immunome had 10,634,245 shares of common stock outstanding.

AOP Orphan reports full validity of arbitral award against PharmaEssentia

On March 25, 2021 PharmaEssentia reported that had repeatedly attempted to terminate the agreement with AOP Orphan concerning BESREMi (Ropeginterferon alfa-2b) (Press release, AOP Orphan Pharmaceuticals, MAR 25, 2021, View Source [SID1234577175]). After two and a half years of arbitral proceedings, in October 2020, the ICC Arbitral Tribunal issued its award in the matter. The arbitral award states that PharmaEssentia’s multiple attempts to terminate the agreement were unjustified, and that AOP Orphan is entitled to payment of damages of approximately EUR 142 million for project delays caused by PharmaEssentia.

In December 2020, PharmaEssentia filed an application to set aside this arbitral award with the Frankfurt Higher Regional Court, arguing that the award violated public order and PharmaEssentia’s right to be heard. The Frankfurt Higher Regional Court, a German court with major experience in handling this kind of proceedings, called a hearing within less than two months of PharmaEssentia’s filing its setting aside application.

Award declared enforceable

Today, the Frankfurt Higher Regional Court announced its decision. As anticipated, the Court dismissed PharmaEssentia’s set aside application, confirming that both parties had sufficient opportunity to be heard, that all evidence brought before the Arbitral Tribunal was duly taken into consideration, and that the public order was fully respected.

Thus, the award as issued by the ICC Arbitral Tribunal in October 2020 has now been declared enforceable by Frankfurt Higher Regional Court, and AOP Orphan can pursue its enforcement in Germany and elsewhere. An appeal to the German Supreme Court is possible but would not hinder the enforcement of the award.

Rudolf Widmann, Chief Therapeutics Development Officer and Member of the Board of AOP Orphan, explains: "AOP Orphan has always complied with its contractual obligations and is entitled to compensation by PharmaEssentia, following their repeated attempts to boycott the joint project and success of BESREMi. We encourage PEC to accept the arbitral award and work towards cooperative efforts to exploit the full value of BESREMi in the interest of patients and stakeholders of both companies. AOP Orphan has tried to find solutions several times – I would have preferred to invest time and money into making this highly promising drug available to patients with blood cancer, instead of investing it into expensive lawsuits."

About BESREMi

BESREMi is a long-acting, mono-pegylated proline interferon (ATC L03AB15). Its unique pharmacokinetic properties offer a new level of tolerability. BESREMi is designed to be conveniently self-administered subcutaneously with a pen once every two weeks, or monthly after stabilization of hematological parameters. This treatment schedule is expected to lead to overall better safety, tolerability and adherence compared to conventional pegylated interferons. Ropeginterferon alfa-2b was discovered by PharmaEssentia, a long-term partner of AOP Orphan. In 2009, AOP Orphan in-licensed the exclusive rights for clinical development and commercialization of Ropeginterferon alfa-2b in PV and other MPNs for European, Commonwealth of Independent States (CIS), and Middle Eastern markets.

Castle Biosciences Announces Publication Demonstrating Dermatologists Are Increasingly Integrating DecisionDx-Melanoma Into Melanoma Clinical Management Decisions

On March 25, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported the publication of a cross-sectional study of dermatologists that found its respondents are increasingly incorporating DecisionDx-Melanoma into the management of their patients with melanoma (Press release, Castle Biosciences, MAR 25, 2021, View Source [SID1234577174]). DecisionDx-Melanoma is Castle’s gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors.

The article, titled "Assessment of the 31-Gene Expression Profile Test by Dermatologists: A Cross-Sectional Survey from National Dermatology Conferences," was published in SKIN: The Journal of Cutaneous Medicine. The cross-sectional study was offered to attendees of two national, virtual dermatology conferences during the end of 2020 and beginning of 2021 to assess the professional understanding, opinions and clinical usage of DecisionDx-Melanoma by dermatologists. Participants were asked questions regarding practice demographics, factors considered prior to ordering DecisionDx-Melanoma, their integration of the test’s results into clinical management and their opinions on the usefulness of the test.

Data from 589 U.S. dermatological clinicians showed:

45% of participants ordered the DecisionDx-Melanoma test in the prior twelve months.
Going forward, 82% of participants were "somewhat to very likely" to order the test, with 66% stating they would recommend the test to a friend or family member as part of their melanoma care.
In melanomas less than or equal to 1.0mm (T1), which make up the majority of melanomas, previous studies have demonstrated that a DecisionDx-Melanoma Class 1A test result (lowest risk) has a 5-year recurrence free survival rate of 96.8%, compared to 64.6% for a Class 2B test result (highest risk). 61% of participants stated they would change their treatment plan in this T1 population with a Class 2B test result.
Participants who use DecisionDx-Melanoma indicated that they use the results to impact follow-up schedules, referrals, surveillance imaging, sentinel lymph node biopsy procedure recommendations and other treatment decisions. These uses largely follow published appropriate-use criteria for the test.
Participants responded that patients gain various benefits from DecisionDx-Melanoma test results, including increased knowledge and understanding (70%), personalized treatment options (58%) and eased uncertainty about the future (59%). Even regarding test results indicating the lowest risk of recurrence (i.e. Class 1A), 66% of participants reported potential benefits for ameliorating patients’ anxiety and 46% reported increasing confidence in their management.
"The sample surveyed demonstrated that dermatology specialists are using DecisionDx-Melanoma in increased numbers, and concluded that melanoma patients whose healthcare providers incorporate DecisionDx-Melanoma into their practice may benefit from decreased anxiety and uncertainty from the improved prognosis, reduced need for unwarranted procedures and optimized healthcare resources for patients who need it most," said study author, Darrell Rigel, M.D., M.S., Clinical Professor at New York University School of Medicine.

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. To predict likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithm, i31-GEP, to produce an integrated test result. i31-GEP is an artificial intelligence-based neural network algorithm (independently validated in a cohort of 1,674 prospective, consecutively tested patients with T1-T4 cutaneous melanoma) that integrates the DecisionDx-Melanoma test result with the patient’s traditional clinicopathologic features. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. Through December 31, 2020, DecisionDx-Melanoma has been ordered more than 68,920 times for use in patients with cutaneous melanoma.