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Publication in Cancer Research demonstrates Crescendo Biologics’ Humabody® VH therapeutics outperform conventional antibodies in vivo

On January 15, 2020 Crescendo Biologics Ltd (Crescendo), the drug developer of novel, targeted, T cell enhancing therapeutics, reported the publication of a paper that demonstrates greater tissue penetration and in vivo efficacy of Humabody VH therapeutics compared to conventional antibody formats, in the scientific journal Cancer Research a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Crescendo Biologics, JAN 15, 2020, View Source [SID1234553230]).

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The full paper by Nessler et al can be accessed online HERE.

The study run by Dr Greg M. Thurber at the University of Michigan demonstrates that the level of tissue penetration by Humabodies plays a major role in therapeutic efficacy and illustrates the benefits of using an albumin-binding domain to extend serum circulation time.

Humabodies are small, in vivo matured human VH domain building blocks that can be easily assembled into multifunctional molecules. They can be configured for optimal target engagement in ways which can be challenging for regular antibody formats. Dr Thurber’s results confirm that the smaller size and specifically tailored binding configuration achievable with Humabody molecules can result in improved penetration into the tumour microenvironment and a greater cancer-killing effect using a preclinical in vivo model of prostate cancer.

Dr Greg M. Thurber, an associate professor of chemical engineering and biomedical engineering at the University of Michigan, said:

"The tissue and cellular distribution of biologics is an important but understudied area in drug development. In collaboration with Crescendo, we demonstrated that the distribution of these drugs within the tumor was as significant as the total tumor dose in determining response. Importantly, this work shows how antibody engineering strategies can be used to design therapeutics with improved distribution to maximize efficacy."

Dr James Legg, SVP R&D at Crescendo Biologics, noted that:

"We’re delighted to be working with Greg Thurber’s team at the University of Michigan; they have developed a deep mechanistic understanding and expertise in the in vivo distribution of therapeutic agents. We look forward to continuing our collaboration."

Clovis Oncology’s Rubraca® (rucaparib) Granted FDA Priority Review for Advanced Prostate Cancer

On January 15, 2020 Clovis Oncology, Inc. (NASDAQ: CLVS) reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental New Drug Application (sNDA) for Rubraca (rucaparib) and granted priority review status to the application with a Prescription Drug User Fee Act (PDUFA) date of May 15, 2020. Clovis submitted the sNDA submission for rucaparib as a monotherapy treatment of adult patients with BRCA1/2-mutant recurrent, metastatic castrate-resistant prostate cancer in November 2019 (Press release, Clovis Oncology, JAN 15, 2020, View Source [SID1234553229]).

"Recently presented data suggests that Rubraca may play a meaningful role in the treatment of patients withBRCA1/2-mutant recurrent, metastatic castrate-resistant prostate cancer, and this filing represents an important milestone for Clovis as it brings us one step closer to potentially making this valuable therapy available," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We are encouraged by the FDA’s decision to grant priority review to the Rubraca application, which focuses on eligible patients with advanced prostate cancer, for whom new treatment options are very much needed."

A priority review designation is granted to proposed medicines that the FDA has determined have the potential, if approved, to offer a significant improvement in the safety or effectiveness of the treatment, prevention or diagnosis of a serious condition. Priority designation shortens the review period from the standard 10 months to six months.

About Prostate Cancer

The American Cancer Society estimated that more than 175,000 men in the United States would be diagnosed with prostate cancer in 2019, and the GLOBOCAN Cancer Fact Sheets estimated that approximately 450,000 men in Europe were diagnosed with prostate cancer in 2018. Castrate-resistant prostate cancer has a high likelihood of developing metastases. Metastatic castrate-resistant prostate cancer, or mCRPC, is an incurable disease, usually associated with poor prognosis. Approximately 43,000 men in the U.S. are expected to be diagnosed with mCRPC in 2020. According to the American Cancer Society, the five-year survival rate for mCRPC is approximately 30 percent. Up to 12 percent of patients with mCRPC harbor a deleterious germline and/or somatic mutation in the genes BRCA1 and BRCA2.These molecular markers may be used to select patients for treatment with a PARP inhibitor.

About Rubraca (rucaparib)

Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian and metastatic castration-resistant prostate cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway.

Rubraca U.S. FDA Approved Indications

Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Rubraca is indicated as monotherapy for the treatment of adult patients with deleterious BRCA mutations (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies and selected for therapy based on an FDA-approved companion diagnostic for Rubraca.

Select Important Safety Information

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) occur uncommonly in patients treated with Rubraca, and are potentially fatal adverse reactions. In approximately 1100 treated patients, MDS/AML occurred in 12 patients (1.1%), including those in long-term follow-up. Of these, five occurred during treatment or during the 28-day safety follow-up (0.5%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 28 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA-damaging agents. Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1).

Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose (see Dosage and Administration [2.2] in full Prescribing Information) and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks, or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample cytogenetic analysis. If MDS/AML is confirmed, discontinue Rubraca.

Based on its mechanism of action and findings from animal studies, Rubraca can cause fetal harm when administered to a pregnant woman. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Rubraca.

Most common adverse reactions in ARIEL3 (≥ 20%; Grade 1–4) were nausea (76%), fatigue/asthenia (73%), abdominal pain/distention (46%), rash (43%), dysgeusia (40%), anemia (39%), AST/ALT elevation (38%), constipation (37%), vomiting (37%), diarrhea (32%), thrombocytopenia (29%), nasopharyngitis/upper respiratory tract infection (29%), stomatitis (28%), decreased appetite (23%) and neutropenia (20%).

Most common laboratory abnormalities in ARIEL3 (≥ 25%; Grade 1–4) were increase in creatinine (98%), decrease in hemoglobin (88%), increase in cholesterol (84%), increase in alanine aminotransferase (ALT) (73%), increase in aspartate aminotransferase (AST) (61%), decrease in platelets (44%), decrease in leukocytes (44%), decrease in neutrophils (38%), increase in alkaline phosphatase (37%) and decrease in lymphocytes (29%).

Most common adverse reactions in Study 10 and ARIEL2 (≥ 20%; Grade 1–4) were nausea (77%), asthenia/fatigue (77%), vomiting (46%), anemia (44%), constipation (40%), dysgeusia (39%), decreased appetite (39%), diarrhea (34%), abdominal pain (32%), dyspnea (21%) and thrombocytopenia (21%).

Most common laboratory abnormalities in Study 10 and ARIEL2 (≥ 35%; Grade 1–4) were increase in creatinine (92%), increase in alanine aminotransferase (ALT) (74%), increase in aspartate aminotransferase (AST) (73%), decrease in hemoglobin (67%), decrease in lymphocytes (45%), increase in cholesterol (40%), decrease in platelets (39%) and decrease in absolute neutrophil count (35%).

Co-administration of Rubraca can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring. Because of the potential for serious adverse reactions in breast-fed children from Rubraca, advise lactating women not to breastfeed during treatment with Rubraca and for 2 weeks after the last dose. You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Clovis Oncology, Inc. at 1-844-258-7662.

Emendo Biotherapeutics Raises $61 Million to Advance Next Generation Genome Editing Therapeutics

On January 15, 2020 Emendo Biotherapeutics, a leader in next-generation gene editing using synthetic biology to address untreatable diseases, reported a Series B investment totaling $61 million led by AnGes, Inc., a Japan-based biopharma, reflecting its strategic interest in partnering with Emendo on the development of specific indications (Press release, Emendo Biotherapeutics, JAN 15, 2020, View Source [SID1234553228]).

"This financing provides a strong foundation from which we can accelerate our proprietary OMNI gene editing platform towards a broad clinical pipeline for addressing devastating untreatable diseases," said Dr. David Baram, President & CEO, Emendo Biotherapeutics. "We are grateful for such strong support from so many high-quality investors and strategic partners including AnGes, OrbiMed Advisors, OrbiMed Israel Partners and Takeda Ventures who share our vision to translate this powerful science into transformative medicines."

Emendo Biotherapeutics is pioneering OMNI, a next-generation allele-specific gene editing platform that uses synthetic biology to expand what is possible in genome-editing. In 2019, Emendo granted an option to Takeda to use the OMNI nuclease gene editing program for two research and development targets. Emendo received an undisclosed investment from Takeda Ventures that was converted in the Series B.

Emendo’s OMNI technology enables precision gene editing while maintaining high efficiencies, uniquely addressing dominant indications such as Severe Congenital Neutropenia (SCN), caused by mutations in the neutrophil elastase gene ELANE. Dominant indications represent the vast majority of genetic diseases which until now have been untreatable.

Astellas Completes Acquisition of Audentes Therapeutics

On January 15, 2020 Astellas Pharma Inc. (TSE: 4503) (President and Chief Executive Officer: Kenji Yasukawa, Ph.D., "Astellas") reported that it has successfully completed the previously announced acquisition of Audentes Therapeutics, Inc. ("Audentes"), through a tender offer by its indirect wholly-owned subsidiary Asilomar Acquisition Corp. ("Asilomar") for all of the issued and outstanding shares of common stock of Audentes for a price of US$60.00 per share net to the seller in cash ("Tender Offer") and the subsequent merger of Asilomar with and into Audentes (Press release, Astellas, JAN 15, 2020, View Source [SID1234553227]). Astellas commenced the Tender Offer on December 16, 2019, New York City time, and the Tender Offer expired at 12:00 midnight, New York City time, at the end of the day on January 14, 2020. As of the expiration of the Tender Offer, 35,852,857 shares of Audentes common stock were validly tendered and not properly withdrawn, representing approximately 76.7% of the shares of Audentes common stock outstanding, and such shares have been accepted for payment under the terms of the Tender Offer. The acquisition positions the combined company to become a global leader in AAV-based genetic medicines.

"The Audentes team is comprised of highly talented individuals with world-class expertise in AAV-based genetic medicines manufacturing, research and development, and commercialization," said Kenji Yasukawa, President and CEO, Astellas. "We look forward to working with Audentes to accelerate and expand our efforts in genetic medicines, and to leverage this innovative science to create significant value for patients."

Within Astellas, Audentes will operate as a wholly-owned subsidiary, and will serve as the Center of Excellence for the newly created Genetic Regulation Primary Focus, providing leadership for AAV pipeline advancement through commercialization, manufacturing expansion, and next-generation research initiatives. Effective immediately, Natalie C. Holles has been appointed President and Chief Executive Officer of Audentes.

"Today marks the start of an exciting new chapter for Audentes. By joining the Astellas group of companies, we are confident we can achieve our mandate to expand the breadth and scope of our work to new geographies and patient populations," stated Natalie C. Holles, President and Chief Executive Officer, Audentes. "Now backed by the substantial resources and global footprint of Astellas, we remain focused on achieving our goal of submitting a Biologics License Application (BLA) for AT132 for the treatment of X-linked Myotubular Myopathy to the U.S. Food and Drug Administration later this year, advancing the new combined pipeline, and building a world-class genetic medicines company."

Astellas is currently reviewing the impact that the completion of the transactions described above may have on its consolidated business forecast for the current fiscal year and will make any necessary disclosure in accordance with applicable requirements.

Acorda Provides 2019 Highlights and 2020 Guidance at J.P. Morgan Healthcare Conference

On January 15, 2020 Acorda Therapeutics, Inc. (Nasdaq: ACOR) reported 2019 highlights and 2020 guidance and priorities at the 38th Annual J.P. Morgan Healthcare Conference in San Francisco (Press release, Acorda Therapeutics, JAN 15, 2020, View Source [SID1234553225]).

"The approval and launch of INBRIJA was an important milestone for Acorda; we believe this product will become a standard of care in the treatment of OFF episodes in Parkinson’s Disease," said Ron Cohen, M.D., Acorda’s President and CEO. "In 2020, we plan to build on our experience from the first nine months of launch, focused on driving patient demand for INBRIJA."

Dr. Cohen continued, "In 2019, we also took important steps toward strengthening our capital structure and improving our balance sheet by implementing a corporate restructuring in October, reducing 2020 expenses by about $60 million, and restructuring our convertible debt. Notably, we successfully exchanged $276 million notional value of 2021 convertible notes, at a 5% discount, for $207 million of December 2024 notes, convertible at a significant premium, and $55 million of cash. We are also working to identify additional opportunities to manage costs. These actions have positioned Acorda to deliver long-term value for our shareholders."

2019 Financials

AMPYRA (dalfampridine) Extended Release Tablets, 10 mg net revenue for 2019 of $162.6 million (unaudited).
INBRIJA (levodopa inhalation powder) net revenue for 2019 of $15.3 million (unaudited).
Product net revenue for 2019 of $178 million, with total revenue of approximately $188 million (unaudited). Product revenue excludes royalty revenue, primarily Fampyra royalty revenue obligations owed to Healthcare Royalty Partners.
The Company continues to expect full year non-GAAP 2019 operating expense of $240 – $250 million. This is a non-GAAP projection that excludes restructuring costs and share-based compensation as more fully described below under "Non-GAAP Financial Measures".
In December 2019, the Company successfully exchanged $276 million notional value of 2021 convertible notes.
2019 year-end cash, cash equivalents, short term investments and restricted cash were approximately $169 million (unaudited). Restricted cash includes $42.7 million in escrow related to the 6% semi-annual interest portion, payable in cash or stock, of the convertible note exchange completed in Q4 2019. If the Company elects to pay interest due in stock, the cash equivalent will be released from escrow.
Final results are subject to completion of the Company’s year-end audit.
Financial Guidance

Total product net revenue for the full year 2020 is expected to be $120 – $150 million, with total revenue expected to be $130 – $160 million.
INBRIJA net revenue for the full year 2020 is expected to be $35 – $40 million.
Expected INBRIJA U.S. annual peak sales has been revised to $300 – $500 million
AMPYRA net revenue for the full year 2020 is expected to be $85 – $110 million.
Operating expenses for the full year 2020 are expected to be $170 – $180 million, reduced from previous guidance of $180 – 190 million. This guidance is a non-GAAP projection that excludes restructuring costs and share-based compensation as more fully described below under "Non-GAAP Financial Measures."
Presentation/Webcast Details

Dr. Cohen will present at the 38th Annual J.P. Morgan Healthcare Conference in San Francisco on Thursday, January 16 at 9:30am PST / 12:30pm EST.

A live audio webcast of the presentation can be accessed under "Investor Events" in the Investor section of the Acorda website at www.acorda.com, or you may use the link:

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