On May 15, 2020 Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported that the U.S. Food and Drug Administration (FDA) has issued a complete response letter (CRL) for the new drug application of avapritinib for the treatment of adults with unresectable or metastatic fourth-line gastrointestinal stromal tumor (GIST) (Press release, Blueprint Medicines, MAY 15, 2020, View Source [SID1234558143]). The CRL states that the FDA cannot approve the application.

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As previously announced, Blueprint Medicines plans to continue to commercialize AYVAKIT (avapritinib) in the United States for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations, and seek marketing approval for avapritinib for the treatment of this patient population in additional geographies, including the European Union. In addition, Blueprint Medicines continues to advance development of avapritinib for the treatment of systemic mastocytosis (SM). Based on top-line results reported in April 2020 for Blueprint Medicines’ Phase 3 VOYAGER trial, the company previously announced plans to discontinue further development of avapritinib in GIST indications other than PDGFRA exon 18 mutant GIST.

About AYVAKIT (avapritinib)

AYVAKIT (avapritinib) is a kinase inhibitor approved by the FDA for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. AYVAKIT is the first precision therapy approved to treat a genomically defined population of patients with GIST and the only highly active treatment for PDGFRA exon 18 mutant GIST. The FDA granted Breakthrough Therapy Designation to avapritinib for the treatment of unresectable or metastatic GIST harboring the PDGFRA D842V mutation. For more information, visit AYVAKIT.com.

Avapritinib is not approved for the treatment of any other indication in the U.S. or any other jurisdiction by the FDA or any other health authority.

Blueprint Medicines is developing avapritinib globally for the treatment of advanced, smoldering and indolent SM. The FDA granted Breakthrough Therapy Designation to avapritinib for the treatment of advanced SM, including the subtypes of aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of avapritinib and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for avapritinib in the rest of the world.

On May 15, 2020 Ribon Therapeutics, a clinical stage oncology company developing first-in-class therapeutics targeting stress response pathways, reported the presentation of new data at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting II, taking place from June 22-24, 2020 (Press release, Ribon Therapeutics, MAY 15, 2020, View Source [SID1234558132]).

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Ribon will present findings from its development program, which includes the following:

Title: PARP7 negatively regulates the Type I interferon response in cancer cells and its inhibition leads to tumor regression
Abstract ID: 3405
Session Type: Minisymposium (oral presentation)
Session Category: Experimental and Molecular Therapeutics
Session Title: Novel Mechanisms Enabled by Tool Molecules
Date/Time: June 23, 2020, 9:00 – 11:00 a.m. EDT
Presenter: Joseph Gozgit, PhD
Title: A bespoke screening platform to study mono(ADP-ribosylation)
Abstract ID: 506 / 2
Session Type: Poster Session
Session Title: Screening, Lead Identification, and Optimization
Date/Time: June 22, 2020, 9:00 a.m. – 6:00 p.m. EDT
Presenter: Tim J. Wigle, PhD
Title: A multi-omic characterization of PARP enzymes in cancer to identify novel monoPARP drug targets
Abstract ID: 4381
Session Type: Poster Session
Session Title: Knowledge, Networks, Graphs, and Models for Discovery
Date/Time: June 22, 2020, 9:00 a.m. – 6:00 p.m. EDT
Presenter: Ryan Abo, PhD
AACR Virtual Meeting II the second of two virtual meetings being held by AACR (Free AACR Whitepaper); the first, AACR (Free AACR Whitepaper) Virtual Meeting I, took place April 27-28, 2020. Presentations from Virtual Meeting I can be accessed at View Source

On May 15, 2020 HiFiBiO Therapeutics reported that have generated preclinical data packages for novel monoclonal antibodies that demonstrate favorable clinical development profiles as new cancer immunotherapeutic options (Press release, HiFiBiO Therapeutics, MAY 15, 2020, View Source [SID1234558131]). The team will present highlights in three poster sessions at the forthcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II, June 22-24, 2020. Taken together, these three programs from the HiFiBiO Therapeutics pipeline are evidence of the maturation of the company’s unique and comprehensive capabilities to uncover disease mechanisms and indications at the single-cell level; apply a deep understanding of immune system biology to select antibodies that present the best prospects for clinical development; and match these high-quality antibodies to the patients who are most likely to derive benefit.

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"We are pleased to have the opportunity to present our work to the oncology research community at AACR (Free AACR Whitepaper) and to share our innovative approach to transform the drug discovery and development paradigm by combining a deep understanding of immune-modulation with a world-leading single-cell platform and integrated analytics. By applying this approach over the past two and a half years, we have built a sustainable pipeline with high-quality candidates moving rapidly towards clinical studies," said Liang Schweizer, PhD, President and CEO of HiFiBiO Therapeutics.

The three HiFiBiO Therapeutics pipeline programs being presented at the AACR (Free AACR Whitepaper) meeting are:

HFB3010 (OX40)

HFB301001 is a novel, fully human IgG1 class OX-40 agonistic antibody with an optimized pharmacological profile. In contrast to previous anti-OX-40 antibodies, the agonistic activity of HFB301001 is further enhanced in the presence of the endogenous ligand OX-40L, does not result in reduced expression of OX-40 on T cells, and leads to superior anti-tumor activity in a human OX-40 knock-in mouse model compared to a benchmark antibody. Applying innovative biomarker strategy by leveraging its cutting-edge single-cell platform, HiFiBiO Therapeutics is developing the HFB301001 clinical candidate targeting certain patient populations which confer sensitivity towards treatment.

HFB2003 (TNFR2)

HiFiBiO Therapeutics has discovered and is pursuing the development of a first-in-class anti-TNFR2 monoclonal antibody capable of co-stimulating T cell proliferation and inducing strong in vivo anti-tumor immunity. In tumors, TNFR2 is expressed on activated and exhausted T cells. Targeting TNFR2 has the potential to enhance anti-tumor immunity by stimulating T-cell activation and proliferation in the tumor microenvironment. HiFiBiO’s CelliGO platform enabled the identification of diverse anti-TNFR2 antibodies that target different epitopes of the receptor. The candidate HFB200301 preferentially binds to TCR-activated primary CD8 and CD4 T cells as compared to unstimulated T cells and enhances CD3/CD28-induced activation and proliferation. Single agent anti-tumor activity comparable to anti-PD-1 was observed in several mouse tumor models at well-tolerated doses. An acute NHP exploratory study revealed no safety concerns for this novel mechanism. The clinical candidate HFB200301 has favorable developability and PK profiles and is currently at CMC development stage.

HFB2009 (Gal-9)

Galactoside-binding lectin Galectin 9 (Gal-9) is a key pleiotropic immunosuppressive modulator present in the tumor microenvironment. High Gal-9 expression has been reported in several cancer types including hematological malignancies such as AML and ALL, as well as in multiple solid tumors. Neutralization of Gal-9 has the potential to enhance anti-tumor immune response in the tumor micro-environment. HiFiBiO Therapeutics has discovered and is pursuing the development of HFB200902, an anti-Gal-9 neutralizing antibody with first-in-class potential in AML and solid tumors. HFB200902 blocks the interaction of Gal-9 with TIM3 and CD44, two receptors that have been described to mediate Gal-9-immunosuppressive signals in effector and regulatory T cells. As a result, HFB200902 inhibits Gal-9 induced Th1 cell apoptosis and Treg expansion. Anti-tumor activity and increased survival were observed as single agent and in combination with anti-PD1 in a syngeneic tumor model.

HiFiBiO Therapeutics will take innovative approaches to clinical development of these and other candidates in its pipeline, by pairing these novel antibody candidates with patient stratification biomarkers identified using the company’s proprietary DIS approach. This enables the company’s scientists to analyze individual patient cell samples to understand the complex functions and heterogeneity in immune system characteristics and responses among different patient groups, and to define predictive biomarkers that can be used to match the therapeutics to those patients who will most likely benefit from them.

"The challenges of achieving clinical success for immunotherapies are often related to the complex biology of the tumor microenvironment. Our pipeline focuses on targets with roles on multiple immune cell types, and our development strategy hinges on combining candidates with novel biomarkers to ensure a higher probability of clinical success," commented Francisco Adrian, Senior Vice President of Global Research, HiFiBiO Therapeutics.

"Our single-cell technology paired with our unique data analysis capability enables us to identify novel biomarkers derived from particular immune cell types and mechanisms. Using this approach, we should be able to stratify patients using their profiled genotype and phenotype, which predict sensitivity or resistance to treatment with our antibody candidates," said Andreas Raue, Senior Director of Drug Intelligent Science, HiFiBiO Therapeutics.

Registration for the virtual meeting is being offered by AACR (Free AACR Whitepaper) free of charge; more information is available at AACR (Free AACR Whitepaper) Virtual Annual Meeting II.

On May 15, 2020 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported two upcoming virtual poster presentations introducing the first preclinical data from the JTX-1811 program and data on the characterization of treatment emergent ICOS hi CD4 T cells with vopratelimab and their association with durable clinical responses. These posters will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting, being held June 22-24, 2020 (Press release, Jounce Therapeutics, MAY 15, 2020, View Source [SID1234558130]).

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Virtual Poster and Audio Presentation Details:

Title: Preclinical evaluation of JTX-1811, an anti-CCR8 antibody with enhanced ADCC activity, for preferential depletion of tumor-infiltrating regulatory T cells
Author and Audio Presenter: Fabien Dépis, Ph.D., Principal Scientist in Discovery at Jounce Therapeutics, Inc.
Poster Number: 4532
Session Title: Immunomodulatory Agents and Interventions
Date: Monday, June 22, 2020

Title: ICOS hi CD4 T cells emerging on vopratelimab treatment have Th1 central memory characteristics and may contribute to durability of clinical responses
Author and Audio Presenter: Amanda Hanson, B.A., Associate Scientist in Preclinical Sciences at Jounce Therapeutics, Inc.
Poster Number: 5536
Session Title: Immune Response to Therapies
Date: Monday, June 22, 2020

About JTX-1811
JTX-1811 is a monoclonal antibody designed to selectively deplete immuno-suppressive tumor-infiltrating T regulatory (TITR) cells. The target of JTX-1811 is CCR8, a chemokine receptor enriched on TITR cells. When JTX-1811 binds to CCR8, it targets TITR cells for depletion by enhanced antibody-dependent cellular cytotoxicity. Jounce expects to file an Investigational New Drug (IND) application in the first half of 2021.

About Vopratelimab
Jounce’s lead product candidate, vopratelimab, is a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO Stimulator, a protein on the surface of certain T cells found in many solid tumors. Vopratelimab was previously assessed in the Phase 1/2 ICONIC trial and was found to have an acceptable safety profile and be well-tolerated, alone and in combination with each of the anti-PD-1 antibodies nivolumab and pembrolizumab, and ipilimumab, an antibody that binds to CTLA-4. Vopratelimab is currently being assessed in the Phase 2 EMERGE clinical trial in a sequenced combination with ipilimumab in patients with non-small cell lung cancer (NSCLC) who have progressed on or after both a platinum-based regimen and a PD-1 or PD-L1 inhibitor. Jounce is also planning to initiate the Phase 2 SELECT clinical trial of vopratelimab with its investigational PD-1 inhibitor, JTX-4014, in TISvopra biomarker-selected patients who are PD-1 inhibitor naïve in second line NSCLC.

On May 15, 2020 Aprea Therapeutics, Inc. (Nasdaq: APRE), a biopharmaceutical company focused on developing and commercializing novel cancer therapeutics that reactivate mutant tumor suppressor protein, p53, reported financial results for the three months ended March 31, 2020 and provided a business update (Press release, Aprea, MAY 15, 2020, View Source [SID1234558129]).

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"Despite the challenges caused by the emerging COVID-19 pandemic, we continued to make significant progress to advance the development of our lead compound, eprenetapopt. In January 2020 we were granted Breakthrough Therapy Designation by the FDA to support our Phase 3 development program of eprenetapopt in combination with azacitidine," said Christian S. Schade, President and Chief Executive Officer of Aprea. "We are proud of the Aprea team, for their efforts to navigate through these uncharted times to support and advance our aggressive development of both eprenetapopt and our next generation p53 reactivator, APR-548, with minimal interruption."

Business Operations Update:

The Company is conducting, supporting and planning multiple clinical trials of eprenetapopt or APR-246:

·Pivotal Phase 3 MDS Trial—The Company is currently enrolling a pivotal Phase 3 randomized, controlled trial evaluating APR-246 with azacitidine as frontline therapy in HMA-naïve TP53 mutant myelodysplastic syndromes (MDS) patients with a primary endpoint of CR rate. Though the Company had initially observed a decrease in both patient screening and patient enrollment as a result of the coronavirus (COVID-19) pandemic, the Company has recently observed increased patient screening activity and has currently enrolled 140 patients in the trial with a number of additional patients now scheduled for screening. The Company currently plans to close enrollment of this trial in the second quarter of 2020 and remains confident it will have top-line data available by year-end 2020.

·Phase 2 MDS/AML Post-Transplant Trial—The Company is currently enrolling its single-arm, open-label Phase 2 trial evaluating APR-246 with azacitidine as post-transplant maintenance therapy in TP53 mutant MDS and acute myeloid leukemia (AML) patients who have received an allogeneic stem cell transplant. Though the Company had initially observed a decrease in both patient screening and patient enrollment as a result of the COVID-19 pandemic, the Company has recently observed increased patient screening activity and has currently enrolled 16 out of 31 patients in this trial with a number of additional patients scheduled for screening. The Company believes that it will complete enrollment in this trial in the third quarter of 2020.

·Phase 1 AML Trial—Based on in vitro data evidencing synergistic activity between APR-246 and venetoclax, the Company is conducting a Phase 1 clinical trial in frontline and relapsed/refractory TP53 mutant AML assessing APR-246 with venetoclax with or without azacitidine. The goals of the study include determining the safety, tolerability and preliminary efficacy of the combinations. The first patient was enrolled in 1Q 2020 and the Company completed enrollment of the first two safety cohorts of three patients each. Together with its investigators and clinical sites, the Company continues to assess the impact of the COVID-19 pandemic on the enrollment and the ability to maintain patients enrolled in this trial.

·Phase 1 NHL Trial—As further assessment of APR-246 in hematological malignancies, the Company has designed and plans to conduct a Phase 1 clinical trial in relapsed/refractory TP53 mutant chronic lymphoid leukemia (CLL) and mantle cell lymphoma (MCL) assessing APR-246 with venetoclax and rituximab, and APR-246 with ibrutinib. The Company is targeting the first patient to be enrolled in the second half of 2020.

·Phase 1/2 Solid Tumor Trial—Based on in vivo data evidencing synergistic activity between APR-246 and immuno-therapy agents including anti-PD-1 antibody, the Company has designed and plans to conduct Phase 1/2 clinical trials in relapsed/refractory gastric, bladder and non-small cell lung cancers assessing APR-246 with anti-PD-1 therapy. The Company is targeting the first patient to be enrolled in the second half of 2020.

·APR-548 — The Company’s second product candidate, APR-548, is a next-generation p53 reactivator with the potential for oral administration. APR-548 is a unique analog of APR-246 and therefore a pro-drug of MQ. APR-548 exhibits high oral bioavailability in preclinical testing and is being developed in an oral dosage form. The Company has completed Investigational New Drug, or IND, enabling preclinical studies of APR-548 and is targeting the submission of an IND in the first half of 2020.

First Quarter Financial Results

·Cash and cash equivalents: As of March 31, 2020, the Company had $122.5 million of cash and cash equivalents compared to $130.1 million of cash and cash equivalents as of December 31, 2019. The Company expects cash burn for 2020 to be between $35.0 million $40.0 million. The Company believes its cash and cash equivalents as of March 31, 2020 will be sufficient to meet its current projected operating requirements into 2023.

·Research and Development (R&D) expenses: R&D expenses were $9.1 million for the quarter ended March 31, 2020, compared to $3.7 million for the comparable period in 2019. The increase in R&D expenses was primarily related to the advancement of the Company’s lead product candidate, APR-246. In Q1 2019 the Company commenced a pivotal Phase 3 clinical trial of APR-246 with azacitidine for frontline treatment of TP53 mutant MDS which is supported by two ongoing Phase 1b/2 investigator initiated trials, one in the U.S. and one in France, testing APR-246 with azacitidine as frontline treatment in TP53 mutant MDS and AML patients. In addition, in Q1 2020, the Company began enrolling patients in a Phase 1 clinical trial in frontline and relapsed/refractory TP53 mutant AML assessing APR-246 with venetoclax with or without azacitidine.

·General and Administrative (G&A) expenses: G&A expenses were $2.8 million for the quarter ended March 31, 2020, compared to $0.7 million for the comparable period in 2019. The increase in G&A expenses was primarily due to increased insurance and professional fees associated with operating as a public company, as well as increased personnel costs.

·Net loss: Net loss was $9.4 million, or $0.45 per share for the quarter ended March 31, 2020, compared to a net loss of $3.5 million, or $2.97 per share for the quarter ended March 31, 2019. The Company had 21,054,842 shares of common stock outstanding as of March 31, 2020.