On May 20, 2021 Forma Therapeutics Holdings, Inc. (Nasdaq: FMTX) reported that topline interim data from its Phase 2 trial of olutasidenib in relapsed/refractory acute myeloid leukemia (R/R AML) will be presented at the upcoming 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place June 4-8 (Press release, Forma Therapeutics, MAY 20, 2021, View Source [SID1234580390]). Olutasidenib, Forma’s selective inhibitor for cancers with mutations in isocitrate dehydrogenase 1 (IDH1m), demonstrated positive efficacy and a favorable tolerability profile as a monotherapy in patients with IDH1m R/R AML, achieving the primary endpoint of a composite complete remission (CR) or CR plus CR with partial hematologic recovery (CRh) rate of 33.3% (30% CR and 3% CRh).

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The presentation is based on an interim analysis from a pivotal trial arm evaluating continuous treatment with 150 mg twice daily of oral olutasidenib. The data indicate the duration of CR/CRh for people on treatment was 13.8 months. Among patients with a complete remission (CR) who were transfusion-dependent at baseline, 56-day transfusion independence was achieved in 100% of patients as measured by platelets and 83% as measured by red blood cells.

"The data being presented at ASCO (Free ASCO Whitepaper) showcase olutasidenib’s meaningful progress for this patient population, which currently has limited options to extend life expectancy," said Patrick Kelly, M.D., chief medical officer of Forma Therapeutics. "The safety data from the treatment cohort are consistent with the findings from our Phase 1 evaluation in this high-risk AML patient population. The data highlight the duration of response, which is nearly six months longer than current standard of care."

Oral Abstract Session – June 4, 2:30 p.m. ET

Abstract #7006: Effect of olutasidenib (FT-2102) on complete remissions in patients with relapsed/refractory (R/R) mIDH1 acute myeloid leukemia (AML): Results from a planned interim analysis of a phase 2 clinical trial
About the Phase 1/2 Study

The Phase 1/2 study is a multicenter, open-label, multi-cohort evaluation of the safety, efficacy and pharmacokinetics/pharmacodynamics (PK/PD) of olutasidenib for patients with AML or myelodysplastic syndrome (MDS) with an IDH1 mutation. Phase 1 of the trial, 2102-HEM-101, was an open-label, dose-escalation and expansion study of olutasidenib alone and in combination with azacitidine (AZA). The Phase 2 portion was an open-label, fixed-dose study of olutasidenib as a monotherapy and in combination with AZA in multiple IDH1m AML/MDS populations. The primary efficacy evaluable population is comprised of 123 R/R AML patients enrolled in Cohort 1, who received 150 mg of olutasidenib BID at least six months prior to the interim analysis cutoff date of June 18, 2020. The primary endpoint of the Phase 2 pivotal study is a complete remission (CR) plus a complete remission with partial hematological recovery (CRh) that is defined as <5% blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts (platelets >50,000/microliter and ANC >500/microliter).

Key Study Findings

Efficacy (n=123)

Olutasidenib induced a durable CR/CRh rate of 33.3% (95% CI 25.1, 42.2), which is the primary endpoint of the study:
The CR rate was 30.0% (37 of 123 patients) and the CRh rate was 3.0% (4 of 123 patients)
While the median duration of response was not yet reached, in a sensitivity analysis with hematopoietic stem cell transplant considered as the end of a response, the median duration was 13.8 months.
The median duration of overall response was 11.7 months.
The median overall survival (OS) was 10.5 months. The median OS for non-CR/CRh responders was 15.0 months. A median OS has not yet been reached for the CR/CRh population, with an 18-month survival estimate of 87.0%.
Transfusion independence was achieved in all response groups at 56 days, particularly in those achieving CR, with 100% independence for platelet transfusions and 83.0% independence for red blood cells.
Safety (n=153)

Olutasidenib was well-tolerated, with adverse events (AEs) consistent with the late stage disease and the heavily pre-treated population. A safety analysis for all 153 patients enrolled in the Phase 2 Cohort 1 found the most common grade 3/4 (≥ 20% or ≥ 10%) treatment-emergent adverse events (TEAEs) were febrile neutropenia (20%), anemia (19%), thrombocytopenia (16%), neutropenia (13%), leukocytosis (9%) and fatigue (<1%). AEs of interest were the following:
14% of patients reported AEs due to Differentiation syndrome, including 7% Grade 3 and 1% Grade 4 AEs. Most resolved with corticosteroids and treatment interruption. However, 1 fatal event was reported.
8% of patients reported AEs due to QTc prolongation, with <1% Grade 3 or 4. No events led to discontinuation.
Grade 3 or 4 elevation in liver parameters (ALT/AST/total bilirubin) occurred in 10% and 2% of patients, respectively. Most resolved with treatment interruption and dose reduction. Seven patients (<5%) discontinued study treatment due to LFT abnormalities. No Hy’s law cases reported.
About Olutasidenib

Olutasidenib is an oral, potent, small-molecule investigational agent designed to selectively bind to and inhibit mutated IDH1 enzymes. This targeted treatment has the potential to provide therapeutic benefit by reducing 2-HG levels and restoring normal cellular differentiation. With the conclusion of the Phase 2 R/R AML trial, Forma has begun preparing a new drug application (NDA) for submission to the U.S. Food and Drug Administration (FDA).

IDH1 is a natural enzyme that is part of the normal metabolism of all cells; when mutated, its activity can promote blood malignancies and solid tumors. IDH1 mutations are present in 6-8% of patients with AML and as many as 70 to 80% of patients with grade II/III gliomas and secondary glioblastoma. In gliomas, IDH1 mutations occur early in the tumor pathogenesis and persist throughout progression from a neural stem or progenitor cell. Gliomas are the most common, aggressive and difficult-to-treat primary brain tumors, and high-grade gliomas are associated with poor long-term prognosis. Treatment options for relapsed glioma are limited.

On May 20, 2021, Aclaris Therapeutics, Inc. (the "Company") reported that it entered into a Sales Agreement (the "Agreement") with SVB Leerink LLC ("SVB Leerink") and Cantor Fitzgerald & Co. ("Cantor") under which the Company may offer and sell, from time to time at its sole discretion, shares of its common stock, par value $0.00001 per share (the "Common Stock"), having an aggregate offering price of up to $150,000,000 through SVB Leerink and Cantor as its sales agents (Filing, 8-K, Aclaris Therapeutics, MAY 20, 2021, View Source [SID1234580423]). The issuance and sale, if any, of Common Stock by the Company under the Agreement will be made pursuant to a registration statement on Form S-3.

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SVB Leerink and Cantor may sell the Common Stock by any method permitted by law deemed to be an "at the market offering" as defined in Rule 415 of the Securities Act of 1933, as amended. SVB Leerink and Cantor will use commercially reasonable efforts to sell the Common Stock from time to time, based upon instructions from the Company (including any price, time or size limits or other customary parameters or conditions the Company may impose). The Company will pay SVB Leerink and Cantor a commission equal to three percent (3.0%) of the gross sales proceeds of any Common Stock sold through SVB Leerink and Cantor under the Agreement. The Company has provided customary representations, warranties and covenants and the parties have agreed to customary indemnification rights.

The Company is not obligated to make any sales of Common Stock under the Agreement. The offering of shares of Common Stock pursuant to the Agreement will terminate upon the earlier of (i) the sale of all Common Stock subject to the Agreement or (ii) termination of the Agreement in accordance with its terms.

The foregoing description of the Agreement is not complete and is qualified in its entirety by reference to the full text of the Agreement, a copy of which is filed herewith as Exhibit 10.1 to this Current Report on Form 8-K and is incorporated herein by reference.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the securities discussed herein, nor shall there be any offer, solicitation, or sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

On May 20, 2021, Pieris Pharmaceuticals, Inc. (the "Company") and Biotechnology Value Fund, L.P., Biotechnology Value Fund II, L.P., and Biotechnology Value Trading Fund OS, L.P. (collectively, "BVF") reported that entered into an Exchange Agreement (the "Exchange Agreement") pursuant to which BVF agreed to exchange (the "Exchange") an aggregate of 5,000,000 shares of the Company’s common stock, par value $0.001 ("Common Stock"), owned by BVF for an aggregate of 5,000 shares of the Company’s newly-designated Series E Convertible Preferred Stock, a "toothless" preferred stock, par value $0.001 per share ("Series E Preferred Stock") (Filing, 8-K, Pieris Pharmaceuticals, MAY 20, 2021, View Source [SID1234580441]). The Exchange closed on May 21, 2021.

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As described below, the Series E Preferred Stock has substantially the same terms as the Company’s Series D Convertible Preferred Stock, par value $0.001 per share ("Series D Preferred Stock"), issued in March 2020; Series C Convertible Preferred Stock, par value $0.001 per share ("Series C Preferred Stock"), issued in November 2019; Series B Convertible Preferred Stock, par value $0.001 per share ("Series B Preferred Stock"), issued in January 2019; and Series A Convertible Preferred Stock, par value $0.001 per share ("Series A Preferred Stock"), issued in June 2016, all currently held by entities affiliated with BVF. The shares of Series E Preferred Stock issued in the Exchange are convertible into an aggregate of 5,000,000 shares of Common Stock (subject to adjustment as provided in the Series E Certificate of Designation, as defined below), subject to a 9.99% beneficial ownership blocker provision described below.

As of the date of the Exchange Agreement, BVF represented to the Company that it beneficially owned 5,872,762 shares of Common Stock, representing approximately 9.28% of the shares of Common Stock outstanding as of such date. In addition, BVF holds (i) 2,907 shares of Series A Preferred Stock, which are convertible into 2,907,000 shares of Common Stock (subject to adjustment as provided in the Certificate of Designation of Series A Convertible Preferred Stock of Pieris Pharmaceuticals, Inc. (the "Series A Certificate of Designation")), subject to a 9.99% beneficial ownership blocker provision set forth in the Series A Certificate of Designation; (ii) 5,000 shares of Series B Preferred Stock, which are convertible into 5,000,000 shares of Common Stock (subject to adjustment as provided in the Certificate of Designation of Series B Convertible Preferred Stock of Pieris Pharmaceuticals, Inc. (the "Series B Certificate of Designation")), subject to a 9.99% beneficial ownership blocker provision set forth in the Series B Certificate of Designation; (iii) 3,522 shares of Series C Preferred Stock, which are convertible into 3,522,000 shares of Common Stock (subject to adjustment as provided in the Certificate of Designation of Series C Convertible Preferred Stock of Pieris Pharmaceuticals, Inc. (the "Series C Certificate of Designation")), subject to a 9.99% beneficial ownership blocker provision set forth in the Series C Certificate of Designation; and (iv) 3,000 shares of Series D Preferred Stock, which are convertible into 3,000,000 shares of Common Stock (subject to adjustment as provided in the Certificate of Designation of Series D Convertible Preferred Stock of Pieris Pharmaceuticals, Inc. (the "Series D Certificate of Designation")), subject to a 9.99% beneficial ownership blocker provision set forth in the Series D Certificate of Designation.

A copy of the Exchange Agreement is attached hereto as Exhibit 10.1 and is incorporated herein by reference. The foregoing is only a brief description of the material terms of the Exchange Agreement, does not purport to be complete and is qualified in its entirety by reference to the full text of the Exchange Agreement. The representations, warranties and covenants made by the Company in the Exchange Agreement were made solely for the benefit of the parties to the Exchange Agreement, including, in some cases, for the purpose of allocating risk among the parties thereto, and should not be deemed to be a representation, warranty or covenant to investors. Moreover, such representations, warranties or covenants were made as of May 20, 2021. Accordingly, such representations, warranties and covenants should not be relied on as accurately representing the current state of the Company’s affairs

On May 20, 2021 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported interim results from the Phase III IMpower010 study, showing for the first time that treatment with Tecentriq (atezolizumab) following surgery and chemotherapy reduced the risk of disease recurrence or death (disease-free survival; DFS) by 34% (hazard ratio [HR]=0.66, 95% CI: 0.50–0.88) in people with Stage II-IIIA non-small cell lung cancer (NSCLC), whose tumours express PD-L1≥1%, compared with best supportive care (BSC) (Press release, Hoffmann-La Roche, MAY 20, 2021, View Source [SID1234580341]). In this population, median DFS was not yet reached for Tecentriq compared with 35.3 months for BSC.

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In the larger population of all randomised Stage II-IIIA study participants, Tecentriq reduced the risk of disease recurrence or death by 21% (HR=0.79, 95% CI: 0.64–0.96) after a median follow-up of 32.2 months.1 In this population, Tecentriq increased DFS by a median of seven months (42.3 months versus 35.3 months with BSC).1 Safety data for Tecentriq were consistent with its known safety profile and no new safety signals were identified. The full results of IMpower010 will be presented in the lung cancer oral abstract session (Abstract #8500) on Sunday 6 June (08:00–11:00 EDT) at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting.

"These landmark Phase III data demonstrate for the first time that cancer immunotherapy can bring a clinically meaningful improvement to certain people with early lung cancer in the adjuvant setting," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "These results lay the groundwork for a new approach to the treatment of early-stage lung cancer and bring us closer to our goal of providing an effective and tailored treatment option for every person diagnosed with this disease."

The goal of adjuvant therapy is to lower the risk of recurrence and provide the best opportunity for a cure. Still, about half of all patients with Stage I-III NSCLC eventually develop disease recurrence following curative-intent treatment.2 Adjuvant platinum-based chemotherapy is the current standard of care for patients with completely resected early-stage NSCLC (Stage IB-IIIA) who are at a high-risk of disease recurrence or relapse. This treatment provides a modest 4–5% improvement in five-year survival compared with observation.3

Follow-up will continue with planned analyses of DFS in the overall intent-to-treat (ITT) population, including Stage IB patients, which at the time of analysis did not cross the threshold, and overall survival (OS) data, which were immature at the time of interim analysis. In the overall randomised population of study participants, adverse events (AEs) occurred in 92.7% of people receiving Tecentriq, compared with 70.7% of those receiving BSC. Grade 3 or 4 events occurred in 21.8% of people treated with Tecentriq compared with 11.5% in the BSC group; 0.8% of people in the Tecentriq group experienced a Grade 5 AE. As anticipated, the addition of up to one year of Tecentriq following chemotherapy led to a higher number of AEs compared with BSC.

Tecentriq has previously shown clinically meaningful benefit in various types of lung cancer, with five currently approved indications in markets around the world. It was the first approved cancer immunotherapy for front-line treatment of adults with extensive-stage small cell lung cancer (SCLC) in combination with carboplatin and etoposide (chemotherapy). Tecentriq also has four approved indications in NSCLC as either a single agent or in combination with targeted therapies and/or chemotherapies. Tecentriq is available in three dosing options, providing the flexibility to choose administration every two, three or four weeks.

Roche has an extensive development programme for Tecentriq, including multiple ongoing and planned Phase III studies across different settings in lung, genitourinary, skin, breast, gastrointestinal, gynaecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines, as well as studies in metastatic, adjuvant and neoadjuvant settings across various tumour types.

About the IMpower010 study
IMpower010 is a Phase III, global, multicentre, open-label, randomised study evaluating the efficacy and safety of Tecentriq compared with BSC, in participants with Stage IB-IIIA NSCLC (UICC 7th edition), following surgical resection and up to 4 cycles of adjuvant cisplatin-based chemotherapy. The study randomised 1,005 people with a ratio of 1:1 to receive either at most 16 cycles of Tecentriq or BSC. The primary endpoint is investigator-determined DFS in the PD-L1-positive Stage II-IIIA, all randomised Stage II-IIIA and ITT Stage IB-IIIA populations. Key secondary endpoints include OS in the overall study population, ITT Stage IB-IIIA NSCLC.

Efficacy results

PD-L1 ≥1% Stage II-IIIA Randomised Stage II-IIIA ITT
Tecentriq (n=248) BSC (n=228) Tecentriq (n=442) BSC (n=440) Tecentriq (n=507) BSC (n=498)
Median DFS (months) NR 35.3 42.3 35.3 NR 37.2
Stratified HR (95% CI) 0.66 (0.50, 0.88) 0.79 (0.64, 0.96) 0.81 (0.67, 0.99)*
Stratified log-rank p-value (2-sided) 0.004 0.02 0.04
NR, not reached.
* Did not cross significance boundary.

Safety results

Tecentriq BSC
All Grade AEs 92.7% 70.7%
Grade 3-4 AEs 21.8% 11.5%
Grade 5 treatment-related AEs 0.8% n/a
AEs leading to treatment withdrawal 18.2% n/a
n/a, not applicable.

About NSCLC
Lung cancer is one of the leading causes of cancer death globally.4 Each year 1.8 million people die as a result of the disease; this translates into more than 4,900 deaths worldwide every day.4 Lung cancer can be broadly divided into two major types: NSCLC and SCLC. NSCLC is the most prevalent type, accounting for around 85% of all cases.5 NSCLC comprises non-squamous and squamous-cell lung cancer, the squamous form of which is characterised by flat cells covering the airway surface when viewed under a microscope.5

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called Programmed Death Ligand-1 (PD-L1), which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of NSCLC, SCLC, certain types of metastatic urothelial cancer, in PD-L1-positive metastatic triple-negative breast cancer and for hepatocellular carcinoma. In the US, Tecentriq is also approved in combination with Cotellic (cobimetinib) and Zelboraf (vemurafenib) for the treatment of people with BRAF V600 mutation-positive advanced melanoma.

About Roche in cancer immunotherapy
Roche’s rigorous pursuit of groundbreaking science has contributed to major therapeutic and diagnostic advances in oncology over the last 50 years, and today, realising the full potential of cancer immunotherapy is a major area of focus. With over 20 molecules in development, Roche is investigating the potential benefits of immunotherapy alone, and in combination with chemotherapy, targeted therapies or other immunotherapies with the goal of providing each person with a treatment tailored to harness their own unique immune system to attack their cancer. Our scientific expertise, coupled with innovative pipeline and extensive partnerships, gives us the confidence to continue pursuing the vision of finding a cure for cancer by ensuring the right treatment for the right patient at the right time.

In addition to Roche’s approved PD-L1 checkpoint inhibitor, Tecentriq (atezolizumab), Roche’s broad cancer immunotherapy pipeline includes other checkpoint inhibitors, such as tiragolumab, a novel cancer immunotherapy designed to bind to TIGIT, individualised neoantigen therapies and T-cell bispecific antibodies.

On May 20, 2021 Exact Therapeutics AS (Euronext Growth: EXTX), a clinical stage precision medicine company utilizing Acoustic Cluster Therapy (ACT) to harness the power of ultrasound in therapeutic amplification across multiple therapeutic areas and product classes, reported that an abstract describing the background and methodology of its Phase I study, ACTIVATE, has been released for publication at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, Exact Therapeutics, MAY 20, 2021, View Source [SID1234580358]).

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The ACTIVATE Study (NCT04021277) is the first in a series of clinical investigations planned of the Company’s Acoustic Cluster Therapy (ACT) platform technology for targeted therapeutic enhancement.

Abstract Title: Phase I trial of acoustic cluster therapy (ACT) with chemotherapy in patients with liver metastases of gastrointestinal origin (ACTIVATE study)

Oral Abstract Session: Trials in Progress, Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Abstract: TPS3145

Lead Author: Professor Udai Banerji, NIHR Professor of Molecular Cancer Pharmacology at The Institute of Cancer Research and Honorary Consultant in Medical Oncology, The Royal Marsden NHS Foundation Trust.