On May 29, 2019 Arvinas, Inc. (Nasdaq: ARVN), a biopharmaceutical company creating a new class of therapies that degrades disease-causing proteins, reported that its lead PROTAC protein degrader, ARV-110, has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) whose disease has progressed after treatment with two or more systemic therapies (Press release, Arvinas, MAY 29, 2019, View Source [SID1234536646]). ARV-110 is an orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor (AR) protein. ARV-110 is currently being evaluated in a Phase 1 clinical trial designed to evaluate the safety, tolerability, and pharmacokinetics of ARV-110 in men with mCRPC whose disease has progressed after treatment with standard of care therapies.

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"While great strides have been made in the treatment of men with metastatic castration-resistant prostate cancer, current AR-targeted standard of care treatments are less effective in patients whose disease includes increased levels of androgen production or mutations in the androgen receptor," said John Houston, Ph.D., President and Chief Executive Officer of Arvinas. "We believe, due to its ability to iteratively degrade the AR protein, ARV-110 could represent a meaningful new therapy to improve the lives of patients battling mCRPC, and for whom current therapies are not effective. The Fast Track designation by the FDA recognizes the urgency for improved treatments for these patients."

About Metastatic Castration-Resistant Prostate Cancer (mCRPC)
In the United States, prostate cancer is both the second most prevalent cancer in men and the second leading cause of cancer death in men. The American Cancer Society predicts that one in nine men will be diagnosed with prostate cancer in his lifetime. Metastatic castration-resistant prostate cancer (mCRPC) is defined by disease progression despite androgen deprivation therapy and is often correlated with rising levels of prostate-specific antigen (PSA).

Current AR-targeted standard of care treatments for mCRPC are less effective in patients whose disease has increased levels of androgen production, AR gene or gene enhancer amplification, or AR point mutations. Between 15-25% of patients do not respond to second-generation hormone therapies like abiraterone and enzalutamide, and the majority of responsive patients will ultimately become resistant, resulting in poor prognoses for men diagnosed with this devastating condition.

About PROTAC Protein Degraders
Arvinas’ PROTAC protein degraders harness the body’s own natural protein disposal system to degrade disease-causing proteins. PROTAC protein degraders recruit an E3 ligase to tag the target protein with ubiquitin, which directs its degradation through the proteasome, a large protein complex that breaks down the ubiquitinated target protein into small peptides and amino acids. As the target protein is degraded, the PROTAC protein degrader is released and acts iteratively to destroy additional target protein.

PROTAC protein degraders offer numerous potential therapeutic advantages, including broad tissue distribution, routes of administration that include oral delivery, and simpler manufacturing than other new modalities, such as cell-based therapies. Arvinas has developed and optimized a proprietary library of protein targeting ligands, E3 ligase ligands, and linkers, which allow the company to rapidly identify and optimize efficient protein degraders with favorable characteristics for successful drug development.

About ARV-110
ARV-110 is an orally bioavailable PROTAC protein degrader designed to selectively target and degrade androgen receptor (AR) protein. ARV-110 is being developed as a potential treatment for men with mCRPC. ARV-110 has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies. Arvinas believes the differentiated pharmacology of ARV-110, including its iterative activity, has the potential to translate into improved clinical outcomes for patients.

The Phase 1 clinical trial of ARV-110, for men with mCRPC whose disease has progressed after treatment with standard of care therapies, began in 1Q2019. Preliminary clinical data for the trial will be shared in 2H2019, including safety, tolerability, and PK data. Full disclosure of trial information is expected in 1H2020, including prostate-specific antigen (PSA) data and Response Evaluation Criteria in Solid Tumors (RECIST) data.

On May 29, 2019 A first-ever inhibitor of a cancer gene found in some lung, colorectal and other cancers and the effectiveness of chimeric antigen receptor (CAR) T cell therapy for patients with chronic lymphocytic leukemia are just some of the research topics that City of Hope physicians and scientists reported that it will present at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2019 annual meeting May 31 – June 4 in Chicago’s McCormick Place (Press release, City of Hope, MAY 29, 2019, View Source [SID1234536662]).

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More than 38,000 oncology professionals and others will attend the conference to learn about the latest scientific research on cancer treatment, detection and prevention.

"ASCO brings together doctors, nurses and other medical professionals with the important goal of discussing and sharing the latest cancer research and treatment," said Michael Caligiuri, M.D., president of City of Hope National Medical Center and Deana and Steve Campbell Physician-in-Chief Distinguished Chair. "The annual meeting contributes to City of Hope’s deep commitment to developing and implementing the most effective and innovative therapies. City of Hope patients ultimately benefit from the knowledge shared at ASCO (Free ASCO Whitepaper)."

City of Hope doctors and scientists will present oral and poster presentations on a wide array of topics. They include:

First clinical trial testing KRAS G12C inhibitor in lung, colorectal and other cancers

Abstract No: 3003

Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 510, a novel small molecule KRASG12C inhibitor, in advanced solid tumors.

Monday, June 3, 8-11 a.m.

McCormick Place, S406

Marwan Fakih, M.D., professor of City of Hope’s Department of Medical Oncology & Therapeutics Research and medical director of Judy & Bernard Briskin Center for Clinical Research, will present a study on the first in-human trial targeting the KRAS G12C oncogene (a gene that when mutated drives tumor growth), which is found in up to 15% of lung cancer patients and 3% of colorectal cancer patients. City of Hope is one of the leading centers evaluating AMG 510, a targeted therapy that, when taken orally on a daily basis, inhibits the growth of KRAS G12C tumors.

The study examined the safety and efficacy of AMG 510 in 20 patients who continue to take the therapy. Most of the patients had advanced cancer and had taken three or more prior lines of treatment; the majority also had colorectal cancer.

Initial results show that two patients with nonsmall cell lung cancer (NSCLC) had partial remissions and six patients (two with NSCLC and four with colorectal cancer) had cancer that had stop growing.

Results so far have demonstrated that the disease is safe for use in patients and very well-tolerated with minimal side effects.

"This is the first-ever KRAS inhibitor that shows anti-tumor activity," Fakih said. "That is quite significant and depending on future results, it has the potential to be life-changing for patients with KRAS G12C."

Fakih will discuss updated clinical results during his ASCO (Free ASCO Whitepaper) presentation.

CAR T therapy for chronic lymphocytic lymphoma

Abstract No: 7501

TRANSCEND CLL 004: Minimal residual disease (MRD) negative responses after lisocabtagene maraleucel (Liso-Cel; JCAR017), a CD19-directed CAR T cell product, in patients (pts) with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL).

Tuesday, June 4, 9:45 a.m. – 12:45 p.m.

McCormick Place, E451

Tanya Siddiqi, M.D., associate clinical professor of hematology and director of the chronic lymphocytic lymphoma program within City of Hope’s Toni Stephenson Lymphoma Center, will present an oral abstract on a CAR T cell therapy for chronic lymphocytic leukemia (CLL). Lisocabtagene maraleucel, also known as liso-cel and JCAR017, targets CD19-positive cancer cells. There is not a lot of current data on CAR T cell therapies for CLL, which is an incurable but slow, growing chronic cancer.

"At some point, CLL can become more aggressive and resistant to even the new targeted therapies," Siddiqi said. "Therefore, novel therapeutics are needed, especially for patients with high risk disease (having markers like deletion 17p, complex cytogenetics, unmutated IGVH) or those who have not responded to other therapies."

The phase 1 study had 15 evaluable patients who had all received prior therapies, including ibrutinib (a multikinase inhibitor), and whose cancer had returned. Initial data shows that there was no minimal residual disease, or traces of cancer, in about 70% of patients as early as 30 days after receiving the CAR T cells. Seven patients also achieved complete remission. The overall response rate (patients who showed a response to the therapy) at six months was 83%.

Patients also had manageable toxicities, or side effects caused by the treatment; these included low grade cytokine release syndrome and neurotoxicity.

"Our study brings additional information showing that the product is efficacious with manageable toxicities in patients who have progressed after ibrutinib," Siddiqi said.

Siddiqi will also present updated study results at the ASCO (Free ASCO Whitepaper) presentation.

In addition, City of Hope doctors will also speak at plenary and education sessions. They include: Saro Armenian, D.O., M.P.H., a City of Hope pediatric hematologist/oncologist, will discuss pediatric oncology abstracts on Sunday, June 2; Tanya Dorff, M.D., associate clinical professor in City of Hope’s Department of Medical Oncology & Therapeutics Research, will discuss prostate cancer abstracts on Sunday, June 2, and will also speak at an education session on diagnostics and therapeutics for prostate cancer on Friday, May 31; Karen Reckamp, M.D., M.S., co-director of City of Hope’s Lung Cancer and Thoracic Oncology Program, will discuss lung cancer abstracts on Monday, June 3; Alex Herrera, M.D., assistant professor in City of Hope’s Department of Hematology & Hematopoietic Cell Transplantation, will discuss relapsed Hodgkin lymphoma at an education session on Monday, June 3; Kim Margolin, M.D., clinical professor in City of Hope’s Department of Medical Oncology & Therapeutics Research, will discuss immunotherapy for brain metastases at an education session on Tuesday, June 4; and Jasmine Zain, M.D., director of City of Hope’s T cell Lymphoma Program, will discuss non-Hodgkin lymphoma abstracts on Tuesday, June 4.

On May 29, 2019 Myovant Sciences (NYSE: MYOV) ("Myovant"), a clinical-stage healthcare company focused on developing and commercializing innovative therapies for women’s health and prostate cancer, reported that it has commenced an underwritten public offering of $100 million of its common shares (Press release, Myovant Sciences, MAY 29, 2019, https://investors.myovant.com/news-releases/news-release-details/myovant-sciences-announces-100-million-public-offering-common [SID1234536698]). All of the common shares are being offered by Myovant. In connection with this offering, Myovant expects to grant the underwriters a 30-day option to purchase up to an additional $15.0 million of its common shares in the offering on the same terms and conditions. Myovant currently intends to use the net proceeds from the offering primarily to fund its clinical development programs, including the Phase 3 LIBERTY 2 trial in uterine fibroids and heavy menstrual bleeding and the Phase 3 HERO trial in advanced prostate cancer, preparations for potential future regulatory approvals and commercialization of relugolix, as well as for working capital and other general corporate purposes.

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J.P. Morgan Securities LLC, Goldman Sachs & Co. LLC, Cowen and Company, LLC and Evercore Group L.L.C. are acting as joint book-running managers for the offering. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed, or the actual size or terms of the offering.

A shelf registration statement relating to the offered common shares was filed with the Securities and Exchange Commission (SEC) and became effective upon filing on May 24, 2019. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website, located at www.sec.gov. Copies of the preliminary prospectus supplement and accompanying prospectus related to the offering may be obtained, when available, from J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attention: Prospectus Department, by email at [email protected] or by phone at (866) 803-9204, Goldman Sachs & Co. LLC, Prospectus Department, 200 West Street, New York, NY 10282, by email at [email protected], by phone at (866) 471-2526 or by facsimile at (212) 902-9316, Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attn: Prospectus Department, by phone at 1-631-274-2806, or Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, New York, NY 10055, by phone at (888) 474-0200, or by email at [email protected].

This announcement is neither an offer to sell nor a solicitation of an offer to buy any of these securities, and shall not constitute an offer, solicitation, or sale in any jurisdiction in which such offer, solicitation, or sale is unlawful.

On May 29, 2019 Akari Therapeutics, Plc (Nasdaq: AKTX), a biopharmaceutical company focused on innovative therapeutics to treat orphan autoimmune and inflammatory diseases where complement and/or leukotriene systems are implicated, reported its financial results for the first quarter ended March 31, 2019 and recent clinical progress (Press release, Akari Therapeutics, MAY 29, 2019, View Source [SID1234536631]).

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"We have seen positive clinical signals in all three of our new programs in BP, HSCT-TMA and AKC, with rapid improvement in the relevant clinical measures and with no drug-related serious adverse events," said Clive Richardson, Interim Chief Executive Officer of Akari Therapeutics. "Both AKC and BP have further planned clinical readouts this year, providing a potential opportunity to consider advancing both into pivotal trials in 2020 and further supporting the therapeutic role of combined C5 and LTB4 treatment."

First Quarter 2019 and Recent Business Highlights

Pediatric hematopoietic stem cell transplant-related thrombotic microangiopathy (HSCT-TMA).
In March 2019, the Company announced it had a successful Type B, pre-IND meeting with the U.S. Food and Drug Administration (FDA) regarding its proposed pivotal clinical trial program for HSCT-TMA. A pivotal trial for HSCT-TMA with nomacopan is expected to start in the fourth quarter of 2019. This condition has an estimated 80% mortality rate in children with this severe disease, with currently no approved treatments.
Phase II clinical trial in patients with bullous pemphigoid (BP).
During the first quarter, the Company announced initial results from the first three patients with mild-to-moderate BP in the ongoing Phase II trial with nomacopan, dosed daily subcutaneously. The data showed no drug-related adverse events and a rapid improvement in disease such that by day 42 of treatment with nomacopan, the BPDAI global score fell by a mean of 52% and blisters/erosions dropped by a mean of 87%. BP is a severe orphan inflammatory skin disease currently treated primarily with steroids and immunosuppressants which bring with them well-known side effects. The Company anticipates data in mild-to-moderate patients from this study by the fourth quarter of 2019, and extension within the current study to include more severe patients in the second half of 2019.
Phase I/II clinical trial in patients with atopic keratoconjunctivitis (AKC).
In a "first in eye" Phase I/II study in AKC, initial surface of the eye data from the first two patients in the study, treated topically with nomacopan demonstrated no drug-related adverse events. In addition, there was a >35% improvement in composite efficacy score at day 14 of treatment compared to baseline treatment on maximal cyclosporin, the standard of care. The Company is currently in Part A of the study and anticipates progressing into the Part B placebo-controlled efficacy arm by mid-year 2019, with completion of the study by the fourth quarter of 2019.
Expanding pipeline opportunities
The Company is identifying an expanding pipeline of opportunities in diseases where complement and leukotriene pathways are both potentially implicated. For example, at the 2019 Association for Research in Vision and Ophthalmology (ARVO) annual meeting Akari described the role of C5 and LTB4 in an experimental autoimmune uveitis model, underpinning the Company’s plans to develop a clinical back of the eye program.
Upcoming Events and Milestones

HSCT-TMA pivotal clinical trial expected to start in the fourth quarter of 2019.
Mild-to-moderate BP trial results expected in the fourth quarter of 2019.
Expansion of existing BP Phase II clinical trial into the severe patient population expected in the second half of 2019.
Expansion of the AKC Phase I/II trial into Part B placebo-controlled efficacy arm after an independent data review of Part A safety expected mid-year 2019.
Completion of Part B of AKC Phase I/II trial by the fourth quarter of 2019.
Initiate a Phase I clinical trial with new auto-injector pen formulation in the second half of 2019.
First Quarter 2019 Financial Results

Research and development (R&D) income in the first quarter of 2019 was $2.3 million, as compared to R&D expenses of $1.0 million in the same quarter the prior year. This difference is primarily due to the receipt of an R&D tax credit of $4.9 million in the first quarter of 2019, as compared to the receipt of an R&D tax credit of $3.8 million in the first quarter of 2018. Excluding the R&D tax credits in both periods, R&D expenses decreased $2.2 million, or 47%, in the first quarter of 2019 compared to the same period the prior year due primarily to lower expenses for manufacturing as the Company had previously manufactured clinical trial material for supply through 2019.
General and administrative (G&A) expenses in the first quarter of 2019 were $2.3 million, as compared to $3.3 million in the same quarter last year. This decrease was primarily due to lower expenses associated with professional services, personnel and rent, as well as lower stock-based non-cash compensation expense.
Total other expenses for the first quarter of 2019 was $2.6 million, as compared to total other income of $3.0 million in the same period the prior year. This change was primarily due to $5.3 million of higher expense related to the change in the fair value of the stock option liabilities in 2019 compared to 2018, and to higher foreign exchange gains in 2019 as compared to 2018.
Net loss for the first quarter of 2019 was $2.5 million, compared to a net loss of $1.3 million for the same period in 2018. The increase in net loss in the first quarter of 2019 was due primarily to the change in the fair value of the stock option liabilities and foreign exchange gains previously cited, offset by the receipt of a higher R&D tax credit in the first quarter of 2019.
As of March 30, 2019, the Company had cash of $6.1 million, as compared to cash of $5.4 million as of December 31, 2018. During the first quarter of 2019, the Company received an R&D tax credit of $4.9 million.
On September 26, 2018, the Company entered into a securities purchase agreement (the "Purchase Agreement") with Aspire Capital Fund, LLC ("Aspire Capital"), which provides that, upon the terms, Aspire Capital is committed to purchase up to an aggregate of $20.0 million of the Company’s ADSs over the 30-month term of the Purchase Agreement. In consideration for entering into the Purchase Agreement, concurrently with the execution of the Purchase Agreement, the Company issued 30,000,000 ordinary shares to Aspire Capital and sold to Aspire Capital 25,000,000 ordinary shares for $0.02 per share (equivalent to $2.00 per ADS and $500,000). Currently, approximately $1.2 million of the $20.0 million facility has been drawn.

On May 29, 2019 CTI BioPharma Corp. (CTI BioPharma) (NASDAQ: CTIC) reported that management will provide a corporate overview at the Jefferies Global Healthcare Conference at 4:30 p.m. EDT in New York City (Press release, CTI BioPharma, MAY 29, 2019, View Source;p=RssLanding&cat=news&id=2399895 [SID1234536647]).

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Presentation details:

Event:

Jefferies Global Healthcare Conference

Date:

Wednesday, Jun. 5

Time:

4:30 p.m. EDT

The presentation will be webcast live and available for replay from the Investors section of CTI BioPharma’s website at www.ctibiopharma.com.