On February 4, 2021 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, reported results for the quarter ended December 31, 2020 (Press release, MEI Pharma, FEB 4, 2021, View Source [SID1234574646]).

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"We remain well positioned and focused on advancing zandelisib toward commercialization to deliver an improved therapeutic option to people living with B-cell malignancies," said Daniel P. Gold, Ph.D., president and chief executive officer of MEI Pharma. "We anticipate multiple important milestones from the zandelisib program this year, including topline data from our Phase 2 TIDAL study in the fourth quarter as we closely monitor for potential negative impacts related to the ongoing COVID 19 pandemic on the study, as well as more broadly across our business and development pipeline. In addition we look forward to reporting clinical data updates from the ongoing Phase 1b study and the continued expansion of the zandelisib clinical program evaluating additional indications and combinations, in particular the start of the Phase 3 study evaluating zandelisib in combination with rituximab in patients with second line follicular lymphoma around mid-year."

Dr. Gold continued: "Beyond the zandelisib development program, this year we look forward to the potential for more advances across our pipeline, including clinical data updates from the Phase 1 voruciclib program and our plans to advance ME-344 into a Phase 2 pilot study evaluating patients with solid tumors."

Anticipated Calendar Year 2021 Drug Candidate Pipeline Developments

Zandelisib – PI3K delta inhibitor for the treatment of various B-cell malignancies

Completion of enrollment in the Phase 2 TIDAL study evaluating zandelisib as a monotherapy for patients with relapsed or refractor follicular lymphoma followed by the reporting of top line clinical data from the Phase 2 TIDAL study.
Initiation of a second arm in the Phase 2 TIDAL study enrolling patients with relapsed or refractory marginal zone lymphoma.
Initiation of the Phase 3 study of zandelisib in combination with rituximab evaluating follicular and marginal zone lymphoma patients who received one or more prior lines of treatment; this study is intended to act as the required confirmatory study for the potential accelerated approval of zandelisib in patients with relapsed or refractory follicular lymphoma.
Clinical updates for the Phase 1b study of zandelisib, including the combination with zanubrutinib.
Voruciclib – CDK9 inhibitor for the treatment of B-cell malignancies and acute myeloid leukemia

Program updates, including data from the Phase 1 program evaluating voruciclib.
ME-344 – tumor selective mitochondrial inhibitor

Update plans for a potential Phase 2 pilot study of ME-344 in solid tumors.
Recent and Second Quarter Fiscal Year 2021 Corporate Highlights

In January 2021, the Phase 1b trial arm exploring zandelisib in combination with zanubrutinib (marketed as BRUKINSA), developed by BeiGene, Ltd., enrolled the first patient in a disease specific expansion cohort. The phase 1b study arm evaluating the combination is conducted under a clinical collaboration with BeiGene to evaluate safety and efficacy for the treatment of patients with various relapsed or refractory B-cell malignancies.

In January 2021, MEI announced that the Phase 1b trial arm exploring zandelisib in combination with zanubrutinib in collaboration with BeiGene completed the safety evaluation stage in patients with B-cell malignancies and is expanding into disease specific B-cell malignancy cohorts. The Safety Review Committee recommended moving forward with a dosing regimen found to be generally well tolerated and active following a planned safety analysis.

In October 2020, Kyowa Kirin Co. Ltd. and MEI announced that the first patient was dosed in the pivotal Phase 2 study of zandelisib in patients with indolent B-cell non-Hodgkin’s lymphoma (iNHL) without small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), and Waldenström’s macroglobulinemia (WM) in Japan. This Phase 2, multicenter is intended to support regulatory approval in Japan.
Second Quarter Fiscal Year 2021 Financial Results

As of December 31, 2020, MEI had $180.1 million in cash, cash equivalents, and short-term investments with no outstanding debt.
For the quarter ended December 31, 2020, cash provided by operations was $4.1 million compared to $10.5 million used in operations for the quarter ended December 31, 2019. Cash provided by operations in the 2020 period reflects $20.9 million cash received from the Japanese taxing authorities as a refund of withholding tax associated with the Kyowa Kirin commercialization agreement signed in April 2020.
Research and development expenses were $22.2 million for the quarter ended December 31, 2020, compared to $8.3 million for the quarter ended December 31, 2019. The increase was primarily related to increased development costs associated with zandelisib, including increased activity in the TIDAL study and start-up costs related to the Phase 3 study, as well as increased personnel costs to support clinical trial activities.
General and administrative expenses were $5.7 million for the quarter ended December 31, 2020, compared to $4.2 million for the quarter ended December 31, 2019. The increase primarily relates to general corporate expenses and personnel costs incurred during the quarter ended December 31, 2020.
MEI recognized revenue of $9.2 million for the quarter ended December 31, 2020, compared to $1.0 million for the quarter ended December 31, 2019. The increase in revenue primarily related to the license agreement with Kyowa Kirin and included the recognition of fees allocated to research and development obligations, and reflect Kyowa Kirin’s share of zandelisib costs which were $9.9 million for the quarter ended December 31, 2020.
Net loss was $11.5 million, or $0.10 per share, for the quarter ended December 31, 2020, compared to net loss of $20.2 million, or $0.26 per share for the quarter ended December 31, 2019. The Company had 112,527,860 shares of common stock outstanding as of December 31, 2020, compared with 105,998,677 shares as of December 31, 2019.
The adjusted net loss for the quarter ended December 31, 2020, excluding non-cash expenses related to changes in the fair value of the warrants issued in connection with the May 2018 financing (a non-GAAP measure), was $18.5 million, compared to an adjusted net loss of $11.8 million for the quarter ended December 31, 2019.

On February 4, 2021 PierianDx, the global leader in clinical genomics knowledge, reported a partnership with the Belgian Society of Medical Oncology (BSMO) to study the impact of comprehensive genomic profiling (CGP) on clinical outcomes of late-stage cancer patients (Press release, PierianDx, FEB 4, 2021, View Source [SID1234574667]). As part of the study, nine sites across Belgium will use the PierianDx interpretation and reporting solution, Clinical Genomics Workspace (CGW), to help determine the best therapeutic options for treatment.

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Current approaches to precision medicine testing often mean that tests are outsourced to large international organizations or that they are run by independent regional labs, neither of which result in standardized clinical care systems or improved collective knowledge. In response to these challenges, the BSMO has established the BALLETT (Belgian Approach for Local Laboratory Extensive Tumor Testing) study to evaluate the impact of CGP.

CGP uses next-generation sequencing (NGS) to analyze hundreds of genes and biomarkers in tissue samples from biopsies or blood and detect those that are clinically relevant in driving cancer growth. Illumina will provide its CGP panel for tissue samples, TruSight Oncology 500 (TSO500), and NovaSeq 6000 and NextSeq sequencing platforms for the study. Clinical interpretation of the sequencing data will be carried out using the PierianDx Clinical Genomics Workspace (CGW) solution.

CGW provides a streamlined, standardized analysis platform in which EU drug approvals and guidelines are matched to complex genetic variants detected in patient tumor DNA and RNA, all within a GDPR-compliant environment. Using the platform, the nine participating Belgian laboratories can collaboratively review variant pathogenicity and clinical impact for their local samples while also benefiting from the knowledge of other clinical laboratory CGW users from around the world. At the same time, the nine Belgian laboratories will provide this standardized testing and analysis close to the patient’s home, where they receive cancer care, accelerating treatment initiation. As this study will also monitor the patient outcomes during and following treatment, a true indication of those longer-term clinical benefits will be derived.

Dr. Brigitte Maes of the Jessa Hospital in Belgium, Coordinator of BALLETT study said, "As part of Belgium’s broad approach to advancing precision medicine the study will generate valuable insights into the value of CGP versus currently reimbursed sequencing approaches. For example, in addition to genetic mutations that drive cancer formation, CGP will also identify cancers driven by the TMB biomarker which can guide patients towards immunotherapy treatments. This means that the study will give access to additional treatments which may not have been considered through more traditional diagnostic testing."

"Dr. Rakesh Nagarajan, Founder of PierianDx states, "We are ecstatic to be part of this groundbreaking study. The CGW platform is in use by over 25 countries to share knowledge and facilitate better treatments and patient outcomes, and now the clinicians involved in this study will benefit from this collective knowledge while incorporating European-specific data sources, which are curated and maintained by PierianDx." He adds, "Not only will this study measure the impacts of CGP but it will provide a justification, framework, and a blueprint for other clinical laboratories around the world that wish to implement similar initiatives."

On February 4, 2021 Novartis reported that may have jumped out ahead of Merck KGaA with targeted lung cancer med Tabrecta, but the German drugmaker has evened the score (Press release, Merck KGaA, FEB 4, 2021, View Source [SID1234574703]).

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The FDA Wednesday cleared its drug Tepmetko in non-small cell lung cancer patients with MET exon 14 skipping mutations, whether or not they’ve received prior treatments. The mutation affects about 3% to 4% of NSCLC patients and creates an aggressive form of the disease.

Tepmetko will bear a list price of $20,898.60 for a 30-day supply, which is "within the range of other oral oncolytics for advanced NSCLC," a spokesperson said by email.

U.S. regulators based their decision on data from the phase 2 Vision trial, which showed Tepmetko could spur a benefit in 43% of patients. Previously treated patients continued to respond to the drug for a median 11.1 months, while those new to therapy responded for a median 10.8 months.

RELATED: Merck KGaA beats out Novartis with targeted lung cancer nod for Tepmetko in Japan

The FDA’s nod follows up on a positive decision from the Japanese Ministry of Health, Labour and Welfare, which last March became the first global regulator to green-light a MET inhibitor. Since then, though, the FDA has gotten in on the action with its May 2020 go-ahead for Tabrecta, and now Merck will be taking its product toe-to-toe with Novartis’ in the U.S.

While the Swiss pharma giant has the head start, Merck KGaA has its own advantage to tout: once-daily dosing. Tabrecta tablets are given twice daily at a 400 mg dose, while patients take two 225 mg Tepmetko tablets simultaneously just once per day.

"Our focus now is to ensure Tepmetko is accessible to patients in the United States and fully integrated into clinical practice, given the important advance it represents for indicated patients as an oral once-a-day precision medicine," said Danny Bar-Zohar, M.D., global head of development for Merck KGaA’s healthcare business.

RELATED: Novartis beats Merck KGaA to U.S. finish line with targeted lung cancer drug Tabrecta

To do that, though, first Merck KGaA will have to ramp up MET testing—a goal Novartis shares. Testing for the mutation is usually done as part of next-gen lung cancer sequencing, Ameet Mallik, EVP at Novartis Oncology U.S., said an interview last spring, and at that time, only about 35% of U.S. lung cancer patients were receiving that sequencing upfront.

On February 4, 2021 Codiak BioSciences, Inc. (NASDAQ: CDAK), a clinical-stage biopharmaceutical company focused on pioneering the development of exosome-based therapeutics as a new class of medicines, reported pharmacodynamic (PD) activity results from the healthy volunteer portion of its randomized, placebo-controlled, double-blind Phase 1 trial of the company’s clinical candidate, exoIL-12 (Press release, Codiak Biosciences, FEB 4, 2021, View Source [SID1234574613]). Analyses of skin punch biopsies bordering the subcutaneous injection site of exoIL-12 revealed local retention of immunologically detectable IL-12 at the injection site, and localized pharmacological activity as measured by levels of the T cell attractant chemokine, IP-10, in the skin. IL-12 was not detected in plasma at any dose of exoIL-12 tested and plasma IP-10 was only detectable at the highest, 12 µg dose. Results confirmed the desired localization and retention of IL-12 at the injection site for at least 24 hours, as well as prolonged IP-10 production for 8-15 days depending upon dose.

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exoIL-12 is the first engineered exosome therapeutic candidate to be evaluated in humans and one of two Codiak programs currently in clinical development. exoIL-12 was engineered using the company’s proprietary engEx Platform and designed to display functional IL-12 – a potent anti-tumor cytokine – on the exosome surface using the exosomal protein, PTGFRN, as a scaffold.

"We now have clinical evidence in healthy volunteers of local, IL-12-driven pharmacology without detectable systemic exposure to IL-12 or drug-related adverse events for exoIL-12," said Benny Sorensen, M.D., Ph.D., Senior Vice President and Head of Clinical Development, Codiak. "These results further support the target profile that we are hoping to achieve with this candidate and have enabled us to identify the optimal dose for the next phase of our clinical program in patients with active, early-stage CTCL. Moreover, this data further validates the capacity of our engEx Platform to engineer precise properties into our exosome-based therapeutic candidates that potentially expand their therapeutic index."

These results are consistent with Codiak’s preclinical testing and confirm exoIL-12’s target product profile of local drug retention at the injection site, prolonged local pharmacodynamic activity, and lack of systemic IL-12 exposure. Codiak plans to initiate the next portion of the Phase 1 clinical trial, evaluating the safety and efficacy of exoIL-12, in cutaneous T Cell lymphoma (CTCL) patients at the dose of 6 µg, which Codiak believes to be the optimal pharmacologically active dose based upon this healthy volunteer data and prior preclinical data with exolL-12.

"We are pleased with the data we have obtained with exoIL-12 in healthy human volunteers and look forward to the initiation of trials in CTCL patients," said Douglas E. Williams, Ph.D., President and Chief Executive Officer, Codiak. "It is heartening to see one of the founding principles of Codiak validated in the current trial, namely that engineered exosomes can offer the opportunity to tailor therapeutic payloads to provide an active biological response while at the same time limiting unwanted side effects."

Pharmacodynamic Data from Healthy Volunteers

A total of five cohorts each with five subjects were enrolled, randomized 3:2 active drug to placebo, and dosed in the first part of the Phase 1 study. Each cohort received a subcutaneously administered single ascending dose of exoIL-12: 0.3 µg, 1.0 µg, 3.0 µg, 6.0 µg or 12.0 µg, respectively.

Pharmacodynamic (PD) measurements including skin IL-12 levels post-injection and IL-12 receptor-mediated signaling assessed by induction of IP-10, were measured in skin punch biopsies at a 1.5 cm radius from the subcutaneous injection site. Samples were collected immediately prior to dosing (placebo or exoIL-12) and at 24 hours, Day 8 and Day 15 after administration. Results showed detectable IL-12 near the injection site as much as 24 hours post injection at the 6 µg dose. Samples collected at the 8-day and 15-day time points did not have detectable IL-12. In contrast, doses from 1.0 µg to 12µg (not 0.3 µg) showed significant induction of IP-10 production in the skin detectable for 8-15 days confirming robust and durable local pharmacology. At the highest 12 µg dose, IP-10 was also detectable in the plasma, but not at any of the lower doses. As previously described, no detectable IL-12 was present in plasma and no drug-related adverse events were observed across the entire dose range. These results confirm the prolonged, local activation of the IL-12 signaling cascade and give us confidence that 6 µg is the optimal dose to move forward in the next phase of clinical testing in CTCL patients.

During the planned part two of the Phase 1 trial, repeat doses of exoIL-12 at 6 µg will be administered into the lesions of stage IA-IIB CTCL patients. Patients will be monitored for safety, pharmacokinetic, and PD effects through analysis of blood and tumor biopsies, and for local and systemic anti-tumor efficacy using validated CTCL assessment criteria, including CAILS and mSWAT scores. The study is being conducted in the United Kingdom. Given COVID-19-related restrictions involving new study initiation, Codiak is working closely with study sites to open enrollment and commence dosing of patients when allowable and appropriate. Safety, biomarker and preliminary anti-tumor efficacy results are anticipated by the end of 2021.

In prior clinical trials conducted by others of recombinant IL-12 (rIL-12), CTCL patients have shown single-agent treatment responses (56-74% overall response rate and up to 22% complete responses1). However, the utility of rIL-12 has been greatly limited due to serious adverse events caused by systemic exposure. To overcome these limitations, exoIL-12 was designed to facilitate dose control of IL-12 and limit systemic exposure and associated toxicity by localizing IL-12 in the tumor microenvironment (TME) in order to potentially expand the therapeutic index.

There is currently no standard of care treatment for early-stage CTCL. Physicians often employ a variety of non-specific interventions, including repetitive radiation therapy, photo therapy, high-potency steroids and local chemotherapy to inhibit tumor growth and halt disease progression. There is a need for treatments that can induce local as well as systemic anti-tumor activity.

About exoIL-12

exoIL-12 is Codiak’s exosome therapeutic candidate engineered to display fully active IL-12 on the surface of the exosome, using the exosomal protein, PTGFRN, as a scaffold, and designed to facilitate potent local pharmacology at the injection site with precisely quantified doses. By limiting systemic exposure of IL-12 and associated toxicity, Codiak hopes to enhance the therapeutic index with exoIL-12, delivering a more robust tumor response, dose control and an improved safety profile.

Codiak intends to focus development of exoIL-12 on tumors that have, in previous clinical testing, shown clinical responses to rIL-12 used as a monotherapy. This list includes CTCL, melanoma, Merkel cell carcinoma, Kaposi sarcoma, glioblastoma multiforme, triple negative breast cancer, among others.

On February 4, 2021 DURECT Corporation (Nasdaq: DRRX) ("DURECT"), a biopharmaceutical company committed to transforming the treatment of acute organ injury and chronic liver diseases by advancing novel and potentially lifesaving therapies based on its endogenous epigenetic regulator program, reported the pricing of its underwritten public offering of 17,708,333 shares of its common stock (the "Offering") for gross proceeds of approximately $42,500,000, before deducting the underwriting discounts and commissions and other estimated offering expenses payable by DURECT (Press release, DURECT, FEB 4, 2021, https://investors.durect.com/news-releases/news-release-details/durect-corporation-announces-pricing-425-million-public-offering [SID1234574630]). The offering is expected to close on or about February 8, 2021, subject to customary closing conditions. In addition, DURECT has granted the underwriter for the Offering a 30-day option to purchase up to an additional 2,656,249 shares of its common stock.

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Cantor Fitzgerald & Co. is acting as the sole book running manager for the Offering.

The underwriter may offer the shares from time to time for sale in one or more transactions on the Nasdaq Capital Market, in the over-the-counter market, through negotiated transactions or otherwise at market prices prevailing at the time of sale, at prices related to prevailing market prices or at negotiated prices. On February 3, 2021, the last sale price of the shares as reported on the Nasdaq Capital Market was $2.87 per share.

DURECT intends to use the net proceeds of the Offering for general corporate purposes, which may include clinical trials, research and development activities, capital expenditures, selling, general and administrative costs, facilities expansion, and to meet working capital needs.

The Offering is being made pursuant to a "shelf" registration statement on Form S-3 (File No. 333-226518) previously filed by DURECT with the Securities and Exchange Commission (the "SEC") on September 28, 2019 and declared effective by the SEC on October 9, 2018. The Offering is being made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A preliminary prospectus supplement describing the terms of the Offering and the accompanying prospectus have been filed with the SEC. Before you invest, you should read the registration statement, the preliminary prospectus, the documents that DURECT has filed with the SEC that are incorporated by reference into the registration statement, and the other documents DURECT has filed with the SEC for more complete information about DURECT and the Offering. You may get these documents for free by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, copies of the final prospectus and the accompanying prospectus relating to the Offering can be obtained, when available, from Cantor Fitzgerald & Co., Attn: Capital Markets, 499 Park Avenue, 6th floor, New York, NY 10022; Email: [email protected]. The final terms of the offering will be disclosed in a final prospectus supplement to be filed with the SEC.

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