On July 31, 2017 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported that the company has entered into a definitive agreement to purchase the Bruton’s tyrosine kinase (BTK) inhibitor program from Redx Pharma Plc (Press release, Loxo Oncology, JUL 31, 2017, View Source [SID1234519934]). The lead candidate from this program is expected to enter clinical development in 2018.

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"We are excited to add another program to our pipeline that so nicely aligns with our larger strategic vision and capabilities," said Jacob Van Naarden, chief business officer of Loxo Oncology. "The Redx team has created novel chemical matter that selectively and reversibly inhibits BTK, a validated molecular target across numerous B-cell leukemias and lymphomas. It is our belief that the widespread use of covalent BTK inhibitors, such as ibrutinib, will increasingly drive acquired resistance through a mutational event in BTK called C481S, leading to a group of relapsing patients in need of new therapies. Our work suggests that a highly selective, reversible BTK inhibitor can address this emerging unmet need in patients whose disease has progressed on a covalent BTK inhibitor. The development of a highly selective compound in a genetically-defined population is a Loxo Oncology core competency."

Under the terms of the agreement, Loxo Oncology has made a $40M payment to Redx Pharma Plc for the full acquisition of the BTK discovery program, including lead candidate LOXO-305 (formerly RXC005). Loxo Oncology is not subject to milestone or royalty obligations.

LOXO-305 was designed to reversibly bind BTK and preserve activity in the presence of the C481S acquired resistance mutation. Additionally, it was designed to avoid off-target kinases that have complicated the development of both covalent and reversible BTK inhibitors, such as EGFR, BMX, TEC, ITK, BLK, LCK and SRC. LOXO-305 will be entering studies in the coming months to enable submission of an Investigational New Drug (IND) application in 2018.

On July 28, 2017 CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical research and development company specializing in oncology, reported that it has entered into a global strategic license with NantCell, Inc., for the exclusive rights to develop and commercialize aldoxorubicin for all indications (Press release, CytRx, JUL 28, 2017, View Source [SID1234519933]). NantCell, a private subsidiary of NantWorks, LLC, is a clinical stage immuno-oncology company focused on developing novel molecularly targeted therapeutics including antibody, T-cell and NK cell based treatments for patients with cancer.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"We are excited to forge this new relationship with NantCell. They are committed not just to bringing aldoxorubicin to the market for patients with soft tissue sarcomas, but to expand aldoxorubicin’s potential use in combination with both immuno-oncology and cell based therapies to better serve patients suffering from cancer," said Steven A. Kriegsman, CytRx’s Chairman and Chief Executive Officer. "This license and strategic investment will put aldoxorubicin in the hands of a committed partner who pioneered the development of albumin based chemotherapeutics, and will allow CytRx to continue to create new ultra-high potency drug candidates based on our LADR technology platform. Aldoxorubicin will clearly benefit from the first-hand experience of the NantCell management team led by Dr. Patrick Soon-Shiong, who developed and gained regulatory approval under a 505(b)(2) pathway and commercialized Abraxane, an albumin-mediated cytotoxic agent which currently grosses approximately $1 billion in annual sales."

"Aldoxorubicin’s distinct profile makes it the first anthracycline to allow for continuous dosing without increasing cardiac toxicity which would be beneficial for the 17 indications for which doxorubicin is currently approved and other indications where it could provide benefit," stated Dr. Soon-Shiong, NantCell’s Chairman and Chief Executive Officer. "We aim to rapidly incorporate aldoxorubicin into multiple treatment protocols for major tumor types like breast and brain cancers as well as sarcomas."

Under the terms of the license agreement, NantCell made a strategic investment by purchasing $13 million of CytRx common stock at $1.10 per share, representing approximately a 92% premium to CytRx’s most recent market price. CytRx is entitled to receive up to an additional $343 million in milestone payments related to regulatory approvals and commercial milestones for aldoxorubicin. In addition, CytRx will receive increasing double-digit royalties for sales of aldoxorubicin for soft tissue sarcomas and mid to high single digit royalties for all other indications. NantCell will be responsible for all future development, manufacturing and commercialization expenses. CytRx also issued NantCell a warrant to purchase up to 3 million shares of common stock at $1.10 over the next 18 months.

Aldoxorubicin is a rationally-engineered cytotoxic which combines doxorubicin, a widely used chemotherapeutic agent, with a novel linker molecule that binds directly and specifically to circulating albumin, the most abundant protein in the bloodstream. Protein-hungry tumors concentrate albumin, which facilitates the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. Typically, doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Using this acid-sensitive linker technology, aldoxorubicin delivers greater doses of doxorubicin (3 ½ to 4 times). To date, there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of drug well in excess of 6,500 mg/m2 of doxorubicin equivalents. Aldoxorubicin is the first-ever single agent to show superiority over doxorubicin in a randomized clinical trial in first-line soft tissue sarcomas.

In addition, CytRx has amended its long-term loan facility and will make a payment of $5 million to the lender upon the closing of the exclusive global license and strategic investment for aldoxorubicin.

CytRx was represented by Skadden, Arps, Slate, Meagher & Flom LLP on the global license and strategic investment.

On July 28, 2017 NewLink Genetics Corporation (NASDAQ:NLNK) reported consolidated financial results for the second quarter of 2017 and provided updates on its clinical development program for indoximod, NewLink Genetics’ small molecule targeting the IDO pathway with a distinct mechanism of action (Press release, NewLink Genetics, JUL 28, 2017, View Source [SID1234519925]).

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"We continue to focus on indoximod, our leading drug candidate, as it advances into late-stage clinical development," said Charles J. Link, Jr., M.D., Chairman, Chief Executive Officer, and Chief Scientific Officer. "We have made great progress since the end of the first quarter. We have strengthened the IP around this program with the USPTO Notice of Allowances for indoximod salts and prodrug formulations, and NLG802 entered the clinic."

Recent Highlights:

NewLink Genetics recently completed a successful face-to-face meeting with the FDA to review the proposed design for the pivotal trial with indoximod for patients with advanced melanoma.

First patient dosed in the Phase 1 study of NLG802, a novel prodrug of indoximod. NLG802 is a distinct investigational agent targeting the IDO pathway and represents an important step in the Company’s product life-cycle planning.

A Notice of Allowance (NOA) by the US Patent and Trade Office (USPTO) was received in early July for our patent application covering indoximod salts and prodrugs. When issued, this patent will provide exclusivity until 2036 and cover both the formulation of indoximod to be used in the pivotal trial and NLG802.

Phase 2 data from a randomized trial of indoximod in combination with the cancer vaccine, PROVENGE (sipuleucel-T), for patients with metastatic castration resistant prostate cancer (mCRPC) were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 5th. These data showed a statistically significant improvement in radiographic progression-free survival (rPFS) of 10.3 months compared to 4.1 months in the placebo arm, with no difference in adverse events between the two arms.

Phase 1b data from a trial of indoximod in combination with standard of care chemotherapy for patients with newly diagnosed Acute Myeloid Leukemia (AML) were presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress on June 23rd. These early data showed that after one cycle of induction therapy, 7/7 patients who achieved complete response (CR) were seen to have no evidence of minimal residual disease (MRD-neg), suggesting that the addition of indoximod has the potential to reduce the proportion of patients with evidence of leukemia after initial therapy.
Guidance for remainder of 2017:

First patients dosed with novel salt formulation of indoximod.

Updated data from Phase 2 trial of indoximod plus gemcitabine/nab-paclitaxel for patients with metastatic pancreatic cancer to be presented at an oncology meeting in late 2017 or early 2018.

Initiation of a pivotal trial of indoximod in combination with PD-1 checkpoint blockade for patients with advanced melanoma, with the goal of full enrollment by end of 2018.
Financial Results for the Three-Month Period Ended June 30, 2017

Cash Position: NewLink Genetics ended the second quarter with cash and cash equivalents totaling $107.8 million compared to $131.5 million for the year ending December 31, 2016.

R&D Expenses: Research and development expenses were $18.2 million in the second quarter of 2017 compared to $27.4 million in the second quarter of 2016. The decrease was due primarily to a $1.8 million decline in clinical trial spend, a decrease in supplies and other expense of $6.8 million, a decrease in personnel-related spend of $2.2 million, offset by an increase in manufacturing-related spend of $1.3 million, and an increase in licensing and consulting fees of $300,000.

G&A Expenses: General and administrative expenses in the second quarter of 2017 were $8.9 million compared to $9.1 million in the second quarter of 2016. The decrease was due to a decline of $1.0 million in personnel-related spend, offset by an increase of $261,000 in consulting and legal fees, an increase in stock compensation expense of $64,000, and an increase in supplies and other expense of $387,000.

Net Loss: NewLink Genetics reported a net loss of $16.7 million or ($0.57) per diluted share for the second quarter of 2017 compared to a net loss of $32.4 million or ($1.12) per diluted share for the second quarter of 2016.

NewLink Genetics ended the quarter with 29,281,301 shares outstanding.

Financial Guidance and Upcoming Investor Meetings

We expect to end 2017 with approximately $75 million in cash and equivalents, which excludes any cash that may be received from financing.

We look forward to presenting at the Baird Healthcare Conference and the Cantor Fitzgerald Healthcare Conference in September in New York City.