On July 01, 2016 KaloBios Pharmaceuticals, Inc. (OTC:KBIOQ), a developmental stage biopharmaceutical company focused on advancing medicines for patients with neglected and rare diseases, reported that it has emerged from Chapter 11 bankruptcy and has also acquired the rights from Savant Neglected Diseases LLC to develop benznidazole for the treatment of Chagas disease (Press release, KaloBios, JUL 1, 2016, View Source [SID:1234513648]).

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"The Company has risen from the ashes with a great deal of hard work and new thinking on how a biopharmaceutical company can operate and a clear vision to move forward as a successful, positive leader in our industry," said Cameron Durrant, MD, KaloBios chairman and CEO. "As one of the few companies solely focused on neglected and rare diseases, KaloBios will continue to move swiftly and apply itself to the real task of bringing patients crucial treatments they need, but to which they may not have access. We also see a unique opportunity to bring new ideas to address concerns, such as drug pricing, for all stakeholders in healthcare – with our Responsible Pricing Model as just the beginning."

Under the terms of the agreement with Savant, the Company has made an upfront payment of $3 million and issued to Savant a warrant to purchase 200,000 shares of KaloBios common stock. The agreement includes milestones and royalties in connection with the development and potential approval and commercialization of benznidazole. If approved, the Company may receive a Priority Review Voucher.

KaloBios’ reorganization plan was overwhelmingly accepted by its creditors and other stakeholders and thereafter was confirmed by the Delaware bankruptcy court on June 16, 2016.

The exit equity financing of $11 million comes on top of a $3 million debtor-in-possession loan funded in May 2016, with both financings provided by investors Black Horse Capital LP, Black Horse Capital Master Fund Ltd., Cheval Holdings Ltd. and Nomis Bay Ltd. This additional liquidity provides a firm base to support the Company’s operations going forward. In connection with the bankruptcy exit, the debtor-in-possession loan converted into shares of KaloBios common stock.

Black Horse Capital managing member Dr. Dale Chappell will join the KaloBios Board of Directors effective immediately. In addition, current Board member David Moradi has stepped down after helping to successfully guide the company through the bankruptcy process. Dr. Durrant and Ronald Barliant will remain on the Board of Directors. Ezra Friedberg and Timothy Morris will also join the Board of Directors as designees of the investors.

"On behalf of the Board of Directors, I want to thank David for his dedication, perseverance and commitment to KaloBios and its vision to emerge as a truly different kind of biopharmaceutical company. We are well on our way thanks to a clear strategy and an intense period of a lot of hard work by a small, focused and competent team," said Dr. Durrant.

"I am pleased that KaloBios is emerging from Chapter 11 with a clear path forward as a stronger, more focused company," said Mr. Moradi. "This positive outcome for all stakeholders is the result of the tireless efforts of the Company’s Board of Directors, management, employees and advisors over the past several months."

KaloBios will file a report on Form 8-K to the Securities and Exchange Commission within the required timeframe.

About Benznidazole

Benznidazole is an oral anti-parasitic medication used in the treatment of Chagas disease. According to the Centers for Disease Control and Prevention (CDC), an estimated 300,000 people in the United States are infected with Chagas disease, which, if left untreated, can lead to serious and potentially life-threatening cardiovascular, gastro-intestinal and neurological complications. Benznidazole is the standard of care for Chagas disease but is not currently approved by the U.S. Food and Drug Administration (FDA) and is available in the United States only from the CDC under investigational protocols. If approved, it would be the first commercially available benznidazole product for U.S. patients with Chagas disease.

T-cell costimulation typically occurs in a defined microenvironment that is not recapitulated by agonistic antibody therapy (Abstracts, Heat Biologics, JUN 30, 2016, View Source [SID1234517429]). To deliver such stimulation under more favorable conditions, we investigated whether an allogeneic cell-based vaccine that secreted Fc-OX40L, Fc-ICOSL, or Fc-4-1BBL would activate and expand T cells comparably to systemically administered agonist antibodies. Among these costimulators, locally secreted Fc-OX40L provided superior priming of antigen-specific CD8+ T cells, compared to combinations with OX40 antibodies or vaccine alone. Vaccine-expressed Fc-OX40L also stimulated IFNγ, TNFα, granzyme B, and IL2 by antigen-specific CD8+ T cells similarly to OX40 antibodies, without off-target consequences such as proinflammatory cytokine induction. Vaccine-secreted Fc-OX40L increased CD127+KLRG-1- memory precursor cells during the contraction phase, resulting in improved proliferation upon secondary antigen challenge, as compared to OX40 antibody. A cell-based vaccine co-secreting gp96-Ig and Fc-OX40L led to even more pronounced tumor control, complete tumor rejection, and increased tumor antigen-specific T-cell proliferation, including in TILs, as compared to combinations of gp96-Ig vaccine and OX40 antibodies, in mice with established melanoma or colorectal carcinoma. These data suggest that local modulation of the vaccine microenvironment has unexpected advantages over systemic costimulation with agonistic antibodies, which may simplify the clinical translation of such combination immunotherapies into humans.

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On June 30, 2016 OPKO Health, Inc. (NASDAQ:OPK) and Transition Therapeutics Inc. (NASDAQ:TTHI, TSX:TTH) reported the signing of a definitive agreement under which OPKO will acquire Transition Therapeutics, a clinical stage biotechnology company (Press release, Opko Health, JUN 30, 2016, View Source [SID:1234514821]).

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Under the terms of the agreement approved by the Boards of Directors of both companies, Transition Therapeutics security holders will receive approximately 6.4 million shares of OPKO common stock. Based on the moving average price of OPKO common stock for the five trading days preceding the signing of the agreement, the transaction is valued at approximately US$60 million, or US$1.55 per share of Transition Therapeutics common stock, based on current outstanding shares. The companies expect the transaction to close during the second half of 2016, subject to approval of Transition Therapeutics stockholders and other customary conditions.

The Transition Therapeutics clinical portfolio includes:

TT401, a once or twice weekly oxyntomodulin for type 2 diabetes and obesity. We believe TT401 to be the most clinically advanced drug candidate among the new class of GLP1-glucagon receptor dual agonists. In a recently completed phase 2 study of 420 patients with type 2 diabetes, subjects receiving the highest dose of TT401 peptide once weekly demonstrated significantly superior weight loss compared with currently approved extended release exenatide and placebo after 12 and 24 weeks of treatment. TT401 also provided a reduction in HbA1c, a marker of sugar metabolism, similar to exenatide at weeks 12 and 24. TT401 strengthens OPKO’s existing pipeline of oxyntomodulin drug candidates for the treatment of type 2 diabetes and obesity. OPKO’s MOD-6031, currently in a phase 1 study, is a once weekly oxyntomodulin with a proprietary delivery system to slowly release the natural oxyntomodulin, which allows the molecule to penetrate the blood brain barrier. The potential of MOD-6031 to interact with CNS, as well as peripheral receptors, is expected to mimic the natural effect of oxyntomodulin for its effects on satiety and weight loss.
TT701 is a once daily oral selective androgen receptor modulator for patients with androgen deficiency. In a 12-week study of 350 male subjects, it resulted in significantly decreased fat mass and increased lean body mass and muscle strength without significantly changing prostate specific antigen levels. The selective and antagonistic properties of TT701 appear to be well suited to provide anabolic therapeutic benefits to specific patient populations, while potentially avoiding, or even reducing, prostate hypertrophy.
ELND005, a neuropsychiatric drug candidate. ELND005 is an orally administered small molecule that has completed phase 2 clinical studies in Alzheimer’s disease and Down syndrome patients.
"This acquisition provides OPKO with two late stage drug candidates, each of which holds exceptional market potential," stated Phillip Frost, M.D., CEO and Chairman of OPKO. "We believe TT401, a once-weekly dual GLP1/Glucagon agonist that recently showed success in a 420-patient phase 2 study, will complement OPKO’s existing oxyntomodulin product candidate (MOD-6031), which may provide enhanced therapeutic benefit through targeted delivery."

Dr. Frost added, "The selective androgen receptor modulator, TT701, could meet an important need in patients who can benefit from its anabolic effects without the risks associated with testosterone products. We believe it fits well with our Claros 1 point-of-care diagnostic products under development for testosterone and PSA, which could serve as companion diagnostics."

"OPKO is ideally positioned to leverage the potential of Transition’s clinical programs and bring these novel therapeutics to market for the benefit of patients," said Tony F. Cruz, Ph.D., CEO and Chairman of Transition Therapeutics, "Further, OPKO has a strong pipeline of products coming to market that can provide future value for Transition Therapeutics stockholders."

About Transition Therapeutics

Transition Therapeutics is a biopharmaceutical development company advancing novel therapeutics for CNS, metabolic diseases and androgen deficiency indications. The company’s wholly-owned subsidiary, Transition Therapeutics Ireland Limited, has two development programs: CNS drug candidate ELND005 for the treatment of Alzheimer’s disease and Down syndrome; and selective androgen receptor modulator drug candidate TT701. Transition’s lead metabolic drug candidate is TT401 for the treatment of type 2 diabetes and accompanying obesity. For additional information about the Company, please visit www.transitiontherapeutics.com.

On June 30, 2016 Merrimack Pharmaceuticals, Inc. (NASDAQ: MACK) reported a newly presented analysis of the Phase 3 NAPOLI-1 data shows patients treated with ONIVYDE (irinotecan liposome injection), also known as "nal-IRI," in combination with fluorouracil (5-FU) and leucovorin, maintain similar baseline quality of life at 12 weeks despite the addition of a second chemotherapeutic agent when compared to 5-FU and leucovorin alone (Press release, Merrimack, JUN 30, 2016, View Source [SID:1234513642]). These findings were presented in an oral session by Dr. Richard Hubner, an investigator on the NAPOLI-1 trial and a Consultant Medical Oncologist at Christie NHS Foundation Trust, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 18th World Congress on Gastrointestinal Cancer in Barcelona, Spain.

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Previously reported Phase 3 NAPOLI-1 data demonstrate that the ONIVYDE combination regimen significantly improves overall survival and progression-free survival when compared to 5-FU and leucovorin alone1. ONIVYDE in combination with 5-FU and leucovorin was approved by the U.S. Food and Drug Administration (FDA) in October 2015 for the treatment of patients with metastatic adenocarcinoma of the pancreas whose disease progressed after gemcitabine-based therapy. It is the first and only FDA-approved therapy in this setting and was recently designated category 1 status by the National Comprehensive Cancer Network.

"This quality of life analysis of the NAPOLI-1 data underscores the significant clinical benefit the ONIVYDE regimen provides to a patient population with few treatment options," said Dr. Richard Hubner, investigator on the NAPOLI-1 trial and Consultant Medical Oncologist at Christie NHS Foundation Trust. "Fluorouracil and leucovorin is recognized as a well-tolerated therapy for metastatic pancreatic cancer patients. The addition of ONIVYDE, a second chemotherapeutic agent, to this treatment regimen demonstrated significant improvement in median overall survival, progression-free survival and overall response rate2 with little or no impact on baseline quality of life at 12 weeks, as shown in this analysis. This further supports the growing recognition that the ONIVYDE combination regimen is a clinically beneficial treatment option for metastatic pancreatic cancer patients who have progressed on gemcitabine-based therapy."

Methodology and Results:

Effects of nal-IRI (MM-398) ± 5-fluorouracil on quality of life (QoL) in NAPOLI-1: A phase 3 study in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy (Abstract O-004)

Quality of life was assessed using the European Organization for Research and Treatment of Cancer quality of life core questionnaire, which includes functional scales (physical, role, cognitive, emotional and social), symptom scales (appetite loss, constipation, diarrhea, dyspnea, fatigue, insomnia, nausea and vomiting and pain), and a global health and quality of life scale.

Patients completed the European Organization for Research and Treatment of Cancer quality of life core questionnaire at treatment start, every 6 weeks and 30 days post-follow-up visit. A total of 154 patients (ONIVYDE in combination with 5-FU and leucovorin, n=71; 5-FU and leucovorin, n=83) comprised the population for this analysis. Sixty-nine percent (49/71) of patients in the ONIVYDE combination regimen group and 53% (44/83) in the 5-FU and leucovorin group had evaluable data at 12 weeks. No substantial differences are identified in the percentage of patients exhibiting improved, stable or worsening quality of life in the global health status, functional scale or symptom scale scores between the two study arms. The analysis demonstrates that in the NAPOLI-1 study, evaluable patients treated with the ONIVYDE combination regimen were able to maintain quality of life over 12 weeks and there were no significant differences versus the 5-FU and leucovorin-treated patients in quality of life response despite the addition of a second chemotherapeutic agent.

On June 30, 2016 ArQule, Inc. (Nasdaq:ARQL) reported that preliminary data presented at ESMO (Free ESMO Whitepaper) GI demonstrate evidence of anticancer activity, defined by objective response rate and disease control rate in an ongoing phase 1/2 biomarker driven trial with ARQ 087 in intrahepatic cholangiocarcinoma (iCCA) (Press release, ArQule, JUN 30, 2016, View Source [SID:1234513641]). Activity was observed in patients with FGFR2 genetic alterations. ARQ 087 is a multi-kinase inhibitor designed to preferentially inhibit the fibroblast growth factor receptor (FGFR) family.

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The presentation titled "ARQ 087, an Oral Pan-Fibroblast Growth Factor Receptor (FGFR) Inhibitor, in Patients with Advanced and/or Metastatic Intrahepatic Cholangiocarcinoma (iCCA)" can be viewed at www.arqule.com/wp-content/uploads/ARQ-087-iCCA-ESMO-GI-2016.pdf.

Preliminary Data Results from Phase 1/2 iCCA Trial with ARQ 087

The data is comprised of 21 patients dosed with ARQ 087, 14 of which presented with FGFR2 genetic alterations and seven of which did not.
Of the 14 iCCA patients with FGFR2 genetic alterations, 12 patients were evaluable.
Among the 12 evaluable patients with FGFR2 genetic alterations, the objective response rate was 25% (three partial responses) and disease control rate was 75% (three partial responses and six patients with stable disease). Patients were evaluated using Standard RECIST (Response Evaluation Criteria in Solid Tumors).
In addition to the three patients with partial responses, three patients had a minor response, defined as a 15-29% tumor reduction. Durable disease control, defined as greater than 16 weeks, was observed in 50% of patients. Progressive disease was the best response in 25% of the patients.
ARQ 087 showed a manageable safety profile with mostly Grade 1 and 2 adverse events.
This data is derived from the phase 1 and 2 portions of the phase 1/2 trial in iCCA.
"Intrahepatic cholangiocarcinoma is a rare liver cancer with a high mortality rate and limited treatment options," said Dr. Brian Schwartz, Head of Research and Development and Chief Medical Officer at ArQule. "There is scientific evidence that this disease can be caused by a number of different genetic alterations, one being FGFR2, thus making the use of precision medicine essential in treating these patients. The data we presented, while preliminary, are very encouraging and offer evidence that ARQ 087 is active in those patients with a FGFR2 genetic alteration. We look forward to concluding the study late in the third quarter of 2016."

The company has been granted orphan drug designation by the U.S. Food and Drug Administration and European Medicine’s Agency for ARQ 087 in this indication.

About Intrahepatic Cholangiocarcinoma

Cholangiocarcinoma (CCA) is the most common biliary malignancy and the second most common hepatic malignancy after hepatocellular carcinoma (HCC)1. Depending on the anatomic location, CCA is classified as intrahepatic (iCCA), perihilar (pCCA), and extrahepatic (eCCA). iCCA originates from the intrahepatic biliary ductal system and forms an intrahepatic mass. The average age adjusted incidence rate for iCCA is approximately one in 100,000 per year in the United States and Europe2,3.

About FGFR and ARQ 087

ARQ 087 is a multi-kinase inhibitor designed to preferentially inhibit the fibroblast growth factor receptor ("FGFR") family with demonstrated efficacy in FGFR2 genetic alterations. The FGFR pathway is disrupted in several ways in human cancer, thus providing numerous therapeutic targets for an inhibitor of this pathway. ARQ 087 has demonstrated in vivo inhibition of tumor growth and downstream signaling in tumors whose growth is driven by FGFR targets.

Signals of single agent activity with this drug were observed in phase 1a testing. Phase 1b expansion cohorts with ARQ 087 include patients with cholangiocarcinoma and adrenocortical tumors, as well as those with FGFR translocations, amplifications and mutations. Clinical development of ARQ 087 has advanced into phase 2 for intrahepatic cholangiocarcinoma (iCCA) following the observation of two confirmed responses in this patient population in the phase 1 portion of the program.