On August 9, 2017 Cempra, Inc. (Nasdaq:CEMP), a clinical-stage pharmaceutical company focused on developing differentiated anti-infectives for acute care and community settings to meet critical medical needs in the treatment of infectious diseases, reported financial results for the quarter ended June 30, 2017 and provided an update on recent corporate developments (Press release, Cempra, AUG 9, 2017, View Source [SID1234520094]). The company will host a webcast and conference call today at 8:45 a.m. ET.

"We have achieved significant progress with the FDA, reaching an agreement on a smaller, more focused and efficient approach to generating a first cohort of solithromycin safety data to support our response to the CRL," said David Zaccardelli, Pharm.D., acting chief executive officer of Cempra.

"We have also progressed our discussions with the FDA on fusidic acid and the agency has agreed that an additional Phase 3 study, similar in design to the successful Phase 3 study we reported earlier this year, would support potential approval of fusidic acid in ABSSSI. This clarity on both programs is very helpful to us as we progress our next steps," Zaccardelli added.

Second Quarter 2017 and Recent Corporate Highlights

Solithromycin

Community-acquired bacterial pneumonia (CABP)

In the first quarter of 2017, we met with the U.S. Food and Drug Administration (FDA) to discuss the solithromycin complete response letter (CRL) and the FDA reiterated their request for additional clinical safety data prior to approval. Importantly, the FDA has stated that the Phase 3 trials provided evidence that oral and intravenous (IV) solithromycin are effective for the treatment of CABP. The FDA has not requested further efficacy data to support our response to the CRL.

Based on input from the FDA, we proposed a protocol that would obtain safety data from an initial cohort of 6,000 CABP patients treated for five days with oral solithromycin, along with 1,200 CABP patients treated with the standard of care (5:1 randomization), at the time we respond to the CRL. We would subsequently provide follow-on data from an additional 3,000 CABP patients treated for five days with oral solithromycin.

The FDA has communicated to us that this initial cohort of safety data with oral dosing, along with a satisfactory response to the manufacturing items raised in the CRL, would be acceptable to support a response to the CRL for the oral NDA and allow the FDA to evaluate the potential approval of oral solithromycin for CABP.

Inclusion/exclusion criteria have been defined in the safety protocol and incorporate exclusion of patients taking selected concomitant medications which may be associated with higher liver enzyme levels, based on data from the Phase 3 SOLITAIRE-ORAL study.

By eliminating the inclusion of IV formulation data in our initial response to the CRL, we expect to be able to conduct the safety study efficiently with the oral formulation and a dosing regimen that appeared to have a more favorable liver safety profile than IV dosing in our Phase 3 program. This approach also simplifies our response to manufacturing items in the CRL by focusing our response only on oral manufacturing. Additional safety data to support the potential approval of IV solithromycin would need to be provided under a separate study to be discussed with the FDA.

We continue to advance our manufacturing activities for solithromycin at Uquifa and we believe that the time required to accumulate clinical safety data will be the rate-limiting step in our timeline to respond to the CRL.

Based on the completed protocol for the proposed safety study, we are actively engaged with potential government and industry partners to identify non-dilutive funding to support the execution of the study.
Ophthalmic

We have an ongoing ophthalmic development program for solithromycin and are completing preclinical work to support a potential IND filing in 2018.

In the second quarter, we presented data at the annual meeting of the Association for Research in Vision and Ophthalmology highlighting topical ophthalmic formulations of solithromycin in preclinical models of activity, tolerability and pharmacokinetics in the eye.

We are exploring the potential effects of solithromycin to treat ophthalmic bacterial infection as well as dry eye.
Fusidic Acid

Based on the results we announced in the first quarter of 2017 from a successful Phase 3 study of fusidic acid in patients with acute bacterial skin and skin structure infections (ABSSSI), we met with the FDA in the second quarter to discuss the next steps required to bring fusidic acid to patients in the United States.

The FDA has agreed that a second Phase 3 study with a similar design to the first successfully completed Phase 3 study could support potential approval of fusidic acid in patients with ABSSSI. Additionally, a thorough QT and drug interaction studies would be required for an NDA submission.

We are also exploring the potential use of fusidic acid for the long-term oral treatment of refractory bone and joint infections, including prosthetic joint infections, caused by staphylococci, including S. aureus and MRSA. Currently, there is no optimal oral, chronic antibiotic for treating these infections. Enrollment in this 30 patient exploratory, open-label study completed in the second quarter. The primary endpoint of the study is clinical success six months after the start of treatment.
Evaluation of Strategic Business Opportunities

As we have announced in a separate press release today, Cempra and Melinta Therapeutics have entered into a definitive agreement under which Melinta will merge with Cempra.

Financial Results for the Three Months Ended June 30, 2017

For the quarter ended June 30, 2017, Cempra reported a net loss of $12.3 million, or $0.23 per share. During the same period in 2016, Cempra reported a net loss of $24.8 million, or $0.51 per share.

Research and development (R&D) expense in the second quarter of 2017 was $8.5 million, a decrease of 46.7 percent compared to the same quarter in 2016. The lower R&D expense was primarily due to a reduced headcount as a result of the corporate restructuring we implemented in the first quarter of 2017, as well as the completion of all major clinical studies by the end of 2016. General and administrative expense was $4.7 million, a 61.1 percent decrease compared to the quarter ended June 30, 2016, driven primarily by reduced headcount as a result of the reduction in workforce, as well as the discontinuation of commercial launch preparation activities that were ongoing at the same time in 2016.

As of June 30, 2017, Cempra had cash and equivalents of $187.0 million and 52.5 million shares outstanding.

As a result of the corporate restructuring we implemented in the first quarter of 2017, our research and corporate expenses trended significantly downward in the second quarter of 2017 and we expect to reduce second half 2017 expenses by more than 70 percent compared to the second half of 2016. These operating expense assumptions exclude the costs associated with any additional clinical trials with any of our product candidates.

On August 9, 2017 Can-Fite BioPharma Ltd. (NYSE MKT: CANF) (TASE:CFBI), a biotechnology company with a pipeline of proprietary small molecule drugs that address inflammatory and cancer diseases, reported that the Phase II liver cancer clinical trial for Namodenoson (CF102), a novel compound for the treatment of advanced hepatocellular carcinoma (HCC), has successfully enrolled and randomized all 78 patients planned in the clinical trial protocol (Press release, Can-Fite BioPharma, AUG 9, 2017, View Source [SID1234520092]).

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"There is definitely a large unmet medical need for the patient population represented in our trial. These are patients who have not responded to first-line therapy with the current standard of care and experienced further disease progression, in addition to having underlying Child-Pugh Class B cirrhosis. In view of the unique nature of our target population, along with our orphan and fast track status, we believe that success in the current Phase II trial will position us for rapid progress towards registration," stated Can-Fite Medical Director, Dr. Michael Silverman. "We now look forward to confirming the encouraging Phase I/II results, which will pave the way for Can-Fite to bring a new treatment option to patients with advanced liver cancer."

The global Phase II study is being conducted in the U.S., Europe and Israel. Patients with advanced HCC, Child Pugh B, are treated twice daily with 25 mg of oral Namodenoson, the dose found to be the most efficacious in Can-Fite’s earlier Phase I/II study. The primary endpoint of the Phase II study is Overall Survival (OS). Secondary endpoints include Progression Free Survival (PFS), safety, and the relationship between outcomes and A3AR expression. As is standard in this indication, the primary endpoint of OS requires following the entire patient population until the statistically predetermined number of events occur. Can-Fite is following the survival data closely and will perform the survival analysis at the earliest possible opportunity.

Can-Fite’s prior Phase I/II study of Namodenoson in this indication successfully achieved its primary and secondary endpoints, with a good safety profile. Most of the patients enrolled in the Phase I/II study had failed prior treatment with Nexavar (sorafenib), the only drug currently approved for this indication.

Data also showed thatNamodenoson has a liver protective effect that is very unique compared to Nexavar and other drugs under development for HCC which have shown to induce hepato-toxicity.

According to Datamonitor, the market for hepatocellular carcinoma drugs is projected to reach $1.4 billion in 2019. Nexavar annual sales, as reported by Bayer, were €870 million in 2016.

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson is being evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug. Can-Fite has received Orphan Drug Designation for Namodenoson in Europe and the U.S., as well as Fast Track Status in the U.S. as a second line treatment for hepatocellular carcinoma.

On August 9, 2017 AVEO Oncology (NASDAQ:AVEO) reported financial results for the second quarter ended June 30, 2017, and provided a business update (Press release, AVEO, AUG 9, 2017, View Source [SID1234520087]).

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"The second quarter was marked by validating events in each of the three pillars of our global tivozanib strategy: a recommendation for approval of tivozanib in advanced renal cell carcinoma (RCC) by the CHMP, reaching our enrollment target for the Phase 3 TIVO-3 trial in RCC, and the successful advancement to Phase 2, at full dose, of the TiNivo trial, our Opdivo combination trial in RCC," said Michael Bailey, president and chief executive officer of AVEO. "We look forward to several key milestones in the coming quarters, including a final determination from the European Commission (EC) on marketing authorization for tivozanib for RCC, as well as the expected presentation of TiNivo Phase 1 study results this fall and the anticipated readout of TIVO-3 in the first quarter of 2018. We believe that we now have the balance sheet to take AVEO beyond these milestones and into the fourth quarter of 2018. This runway could be extended by additional potential payments of up to $16 million by our European tivozanib partner, EUSA Pharma, related to European regulatory and reimbursement approvals, and double-digit royalty payments on net sales for tivozanib in Europe if the EC grants marketing approval for tivozanib."

Mr. Bailey added: "We also look forward to progress in our earlier pipeline programs, including the initiation of an investigator-sponsored, randomized Phase 2 trial of ficlatuzumab, our potent HGF inhibitory antibody, in combination with cetuximab in patients with cetuximab-resistant, metastatic head and neck squamous cell carcinoma (HNSCC). As presented at the ASCO (Free ASCO Whitepaper) annual meeting this past quarter, this combination demonstrated prolonged progression free and overall survival compared to historical controls in Phase 1."

Recent Updates

Enrollment Target Reached for Pivotal Phase 3 TIVO-3 Study of Tivozanib in RCC. In June 2017, AVEO announced that the Company’s pivotal TIVO-3 trial, a randomized, controlled, multi-center, open-label study to compare tivozanib to sorafenib in subjects with refractory RCC, reached its enrollment target of 322 patients, more than two months ahead of the Company’s initial guidance. A pre-planned futility analysis of the TIVO-3 trial is expected around midyear 2017, with topline data expected in the first quarter of 2018. The TIVO-3 trial, together with the previously completed TIVO-1 trial of tivozanib in the first line treatment of RCC, is designed to support an application seeking regulatory approval of tivozanib in the U.S. as a first and third line treatment for RCC.
$14M in Aggregate Gross Proceeds Secured from Credit Facility and At-the-Market Stock Offerings. In June 2017, AVEO announced that it secured gross proceeds of $14 million through two financing facilities: $5 million through a drawdown of its credit facility with Hercules Capital, Inc. and $9 million from the sale of common stock under its at-the-market issuance sales agreement with FBR & Co, effectively exhausting the balance of that facility.
Positive CHMP Opinion for Tivozanib as a Treatment of Advanced RCC. On June 23, 2017, AVEO announced that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), recommended tivozanib for approval as a treatment for patients with advanced RCC. The CHMP’s recommendation was referred to the EC, which is expected to make its final decision about 67 days from the date of the CHMP’s recommendation. If approved by the EC, marketing authorization for tivozanib will be granted in all 28 countries of the European Union, Norway, Iceland and Liechtenstein. Approval would trigger a $4 million research and development reimbursement payment to AVEO from EUSA Pharma, the European licensee for tivozanib, and AVEO would also be eligible for up to $12 million in additional milestones based on reimbursement approvals.
Phase 1/2 TiNivo Trial of Tivozanib and Opdivo (nivolumab) in RCC Successfully Advanced to Phase 2 Portion. In June 2017, AVEO announced that its Phase 1/2 AVEO-sponsored TiNivo trial evaluating tivozanib in combination with Bristol-Myers Squibb’s anti-PD-1 therapy, Opdivo (nivolumab), in subjects with advanced RCC progressed to the Phase 2 portion of the trial, following completion of the Phase 1 portion, which saw no dose limiting toxicities, a good tolerability profile and promising early signs of activity. The full dose tivozanib regimen of 1.5 mg daily for 21 days, followed by a 7-day rest period, was selected as the recommended Phase 2 dose (RP2D) for the expansion portion of the trial, which is expected to enroll an additional 20 subjects.
Results from Two Investigator-Sponsored Phase 1 Studies of HGF Targeted Antibody Ficlatuzumab Presented at the 2017 ASCO (Free ASCO Whitepaper) Annual Meeting. In June 2017, AVEO announced the presentation of results from two investigator-sponsored Phase 1 studies of ficlatuzumab, a potent hepatocyte growth factor (HGF) inhibitory antibody that binds to the HGF ligand with high affinity and specificity to inhibit HGF/c-Met biological activities, at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The first was a study of ficlatuzumab in combination with the EGFR inhibitor cetuximab in patients with cetuximab-resistant, metastatic HNSCC, which demonstrated a disease control rate, prolonged progression free and overall survival that compared favorably to historical controls, in addition to being well tolerated. The Company announced that a randomized, Phase 2, multicenter, investigator-initiated trial to confirm these findings is expected to initiate in the second half of 2017. The second, ongoing study explored ficlatuzumab in combination with high-dose cytarabine in patients with high risk relapsed or refractory AML, demonstrating early signs of tolerability and activity, including a 50% complete response rate.
Matthew Dallas Appointed Chief Financial Officer. In June 2017, Matthew Dallas joined AVEO as its chief financial officer. In this role, Mr. Dallas is responsible for the Company’s financial strategy and management, and serves on the executive leadership team that governs corporate strategy at AVEO. Mr. Dallas succeeds Keith Ehrlich, who retired from the Company.
Receipt of USPTO Notice of Allowance Related to AV-353. In May 2017, AVEO announced receipt of a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for U.S. patent application number 14/653,684, entitled "notch binding agents and antagonists and methods of use thereof." Allowed under the application are composition of matter and method of use claims related to the Company’s humanized anti-Notch 3 antibodies, including AV-353, a potent inhibitory antibody specific to Notch 3. The Notch 3 pathway is implicated in multiple diseases, including Pulmonary Arterial Hypertension. The U.S. patent scheduled to issue from this application will expire December 19, 2032, with the potential for extension to December 19, 2037.
Second Quarter 2017 Financial Highlights

AVEO ended Q2 2017 with $40.1 million in cash, cash equivalents and marketable securities as compared with $23.3 million at December 31, 2016.
Total collaboration revenue was approximately $0.4 million in Q2 2017 compared with $0.2 million for Q2 2016.
Research and development expense was $6.9 million in Q2 2017 compared with $5.6 million for Q2 2016.
General and administrative expense was $2.3 million in Q2 2017 compared with $1.7 million for Q2 2016.
Net loss for Q2 2017 was $33.3 million, or a loss of $0.30 per basic and diluted share, compared with a net loss of $8.6 million, or a loss of $0.13 per basic and diluted share for Q2 2016. An approximate $23.9 million non-cash loss attributable to the increase in the fair value of the warrant liability was recorded in Q2 2017 that principally resulted from the increase in the stock price that occurred within the quarter. In Q2 2016 the non-cash loss attributable to fair value of the warrant liability was $1.0 million.
Updated Financial Guidance

We believe that our $40.1 million in cash resources would allow us to fund our planned operations into the fourth quarter of 2018. This estimate assumes no receipt of milestone payments from our partners or related payment of potential licensing milestones to third parties, no additional funding from new partnership agreements, no additional equity financings, no debt financings and no further sales of equity under our Sales Agreement with FBR. This estimate also assumes no acceleration in repayment of the term loan by Hercules in the event of non-compliance with the $10.0 million financial covenant.

On August 9, 2017 Array BioPharma Inc. (Nasdaq: ARRY), a biopharmaceutical company focused on the discovery, development and commercialization of targeted small molecule cancer therapies, reported results for its fourth quarter and full year of fiscal 2017 and provided an update on the progress of its key clinical development programs and new partnerships (Press release, Array BioPharma, AUG 9, 2017, View Source [SID1234520085]).

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"With the NDAs filed for binimetinib and encorafenib, we look forward to working with the FDA and EMA as they review our applications," said Ron Squarer, Chief Executive Officer. "The robust PFS benefit together with the attractive tolerability profile demonstrated in COLUMBUS suggest the combination represents a potentially important addition to the MEK/BRAF treatment landscape for patients with BRAF-mutant melanoma."

COLUMBUS PHASE 3 TRIAL: NDAs filed with U.S. Food and Drug Administration (FDA) and MAAs filed with the European Medicines Agency (EMA) for binimetinib and encorafenib; COLUMBUS Part 2 data to be presented at 2017 ESMO (Free ESMO Whitepaper) Congress
On July 5, 2017, Array announced that it submitted two NDAs to the FDA to support use of the combination of binimetinib 45 mg twice daily and encorafenib 450 mg once daily (COMBO450) for the treatment of patients with BRAF-mutant advanced, unresectable or metastatic melanoma. The submissions are supported by data from the pivotal Phase 3 COLUMBUS study. In addition, Array’s European partner, Pierre Fabre, filed the MAAs for binimetininb and encorafenib with the EMA in July 2017.

Part 1 of the COLUMBUS study showed that patients who received COMBO450 had a significantly longer progression free survival (PFS) compared to patients receiving vemurafenib. COMBO450 demonstrated a PFS of 14.9 months compared with 7.3 months observed with vemurafenib [hazard ratio (HR) 0.54, (95% CI 0.41-0.71, P<0.001)]. Part 2 of COLUMBUS was designed specifically to assess the contribution of binimetinib to the combination of binimetinib and encorafenib by reducing the dose of encorafenib to 300mg in the combination arm to allow for a comparison of equal doses across arms. In COLUMBUS Part 2, the primary analysis compared PFS in patients treated with binimetinib 45mg twice daily plus encorafenib 300mg daily (COMBO300) to patients treated with encorafenib 300mg daily as a single agent. In May 2017, Array announced top-line results that showed the mPFS for patients treated with COMBO300 was 12.9 months compared to 9.2 months for patients treated with single agent encorafenib, with HR of 0.77 [95% CI 0.61-0.97, p=0.029]. COMBO300 was generally well-tolerated and reported dose intensity and adverse events (AEs) were consistent with COMBO450 results in COLUMBUS Part 1.

A presentation of COLUMBUS Part 2 results entitled "Results of COLUMBUS Part 2: A Phase 3 Trial of Encorafenib (ENCO) Plus Binimetinib (BINI) Versus ENCO in BRAF-Mutant Melanoma," will take place at the 2017 European Society for Medical Oncology Congress (ESMO 2017) in Madrid, Spain on September 9 at 2:45 pm Central European Summer Time (CEST) (8:45 am EDT). The presentation will include progression free survival, objective response rate (ORR), dose intensity, safety and tolerability.

BEACON CRC PHASE 3 TRIAL: Safety lead-in data to be presented at 2017 ESMO (Free ESMO Whitepaper) and Array’s investor reception on September 9, 2017; Randomized portion of trial enrolling patients
Array is advancing BEACON CRC, a global Phase 3 trial of encorafenib and Erbitux (cetuximab), with or without binimetinib, versus standard of care in patients with BRAF-mutant colorectal cancer (CRC) who have previously received first- or second-line systemic therapy. In May 2017, Array announced that based on an attractive safety profile and with early encouraging clinical activity observed in the 30-patient safety lead-in, the randomized portion of the trial was initiated.

A presentation of data from the safety lead-in entitled "BEACON CRC: Safety Lead-In (SLI) for the Combination of Binimetinib (BINI), Encorafenib (ENCO), and Cetuximab (CTX) in Patients (Pts) with BRAFV600E Metastatic Colorectal Cancer (mCRC)," will take place at ESMO (Free ESMO Whitepaper) 2017 on September 9 from 1:15 – 2:15 pm CEST (7:15 – 8:15 am EDT). The presentation will include details on the safety and tolerability profile of the triplet therapy, encorafenib + binimetinib + cetuximab, as well as preliminary measures of efficacy including ORR and available durability results.

ESMO INVESTOR RECEPTION AND WEBCAST: Array will host an investor reception during ESMO (Free ESMO Whitepaper) 2017 where key opinion leaders in the colorectal cancer field, including Dr. Scott Kopetz, M.D. Anderson and Dr. Axel Grothey, Mayo Clinic will give presentations covering the BRAF-mutant colorectal cancer landscape and data from Array’s BEACON CRC safety lead-in. The presentations will be webcast, for those who wish to participate remotely. Details of the webcast will be posted prior to the event on www.arraybiopharma.com.

Date:
Saturday, September 9, 2017
Time:
4:00-6:00 PM CEST (10:00 am – 12-noon EDT)
Location:
Neuvo Boston Hotel, Madrid, Spain
RSVP:
View Source
BEACON CRC was initiated based on results from a Phase 2 study which included the combination of encorafenib and cetuximab in 50 patients with advanced BRAF-mutant CRC, and presented at the 2016 ASCO (Free ASCO Whitepaper) annual meeting. In this arm, median Overall Survival for these patients exceeded one year, which is more than double several separate historical standard of care published benchmarks for this population. [11-16] The objective response rate (ORR) was 22 percent; historical published benchmarks in this patient population using standard of care regimens range between 4 percent to 8 percent. [14-17]

Worldwide, colorectal cancer is the third most common type of cancer in men and the second most common in women, with approximately 1.4 million new diagnoses in 2012. Of these, nearly 750,000 were diagnosed in men, and 614,000 in women. Globally in 2012, approximately 694,000 deaths were attributed to colorectal cancer. In the U.S. alone, an estimated 135,430 patients will be diagnosed with cancer of the colon or rectum in 2017, and approximately 50,000 are estimated to die of their disease. [5] In the United States, BRAF mutations are estimated to occur in 10 to 15 percent of patients with colorectal cancer and represent a poor prognosis for these patients.[6-9] Based on Array’s historical experience, only a small portion of metastatic BRAF-mutant CRC patients exhibit high levels of microsatellite instability-high (MSI-H).

ONO PHARMACEUTICAL COLLABORATION: New license, development and commercialization partnership for binimetinib and encorafenib initiated in Japan and South Korea
Array entered into a license, development and commercialization partnership with Ono Pharmaceutical for binimetinib and encorafenib. As a result of this agreement, Ono received rights to develop and commercialize binimetinib and encorafenib in Japan and South Korea.

Under the terms of the agreement, Array received an upfront payment of $31.2 million (¥3.5 billion) and retains exclusive commercialization rights for binimetinib and encorafenib in the United States, Canada and Israel. Array is entitled to receive up to an additional $156 million (¥17.3 billion) if certain development and commercial milestones are achieved. A portion of these milestones is related to the Phase 3 BEACON CRC trial. In addition, Array will be eligible for robust, tiered, double-digit royalties based on product sales in Japan and South Korea. Ono obtained the right to conduct clinical trials of binimetinib and encorafenib in Japan and South Korea, as well as participate in all future global development of binimetinib and encorafenib by contributing 12% of those future costs.

NEW CLINICAL COLLABORATIONS WITH MERCK AND BRISTOL-MYERS SQUIBB ANNOUNCED IN MSS CRC: Clinical trials with binimetinib and anti-PD-1 therapy expected to begin in the second half of 2017
Array entered into clinical research collaborations with Merck and Bristol-Myers Squibb to study binimetinib plus anti-PD-1 therapy in patients with microsatellite stable metastatic CRC (MSS CRC). The trial with Merck will investigate the safety, tolerability and efficacy of binimetinib with Merck’s KEYTRUDA (pembrolizumab). The trial with Bristol-Myers Squibb will investigate the safety, tolerability and efficacy of binimetinib in combination with Bristol-Myers Squibb’s Opdivo (nivolumab) and Opdivo + Yervoy (ipilimumab) regimen. Array entered into these collaborations based on the growing body of preclinical and clinical evidence that the immune activity of an anti-PD-1 therapy can be enhanced when combined with a MEK inhibitor, such as binimetinib.

The Phase 1/2 studies are expected to establish recommended dose regimens and explore the preliminary anti-tumor activity of the combinations. Results from these studies, which are anticipated to begin in the second half of 2017, will be used to determine optimal approaches to further clinical development of these combinations. Under the Merck agreement, Merck will act as the sponsor of this clinical trial, and Array will supply Merck with binimetinib for use in the trial. Under the Bristol-Myers Squibb agreement, Array and Bristol-Myers Squibb will jointly support the study with Array acting as the sponsor. The majority of colorectal cancers exhibit microsatellite stability (MSS). [10]

OTHER CLINICAL UPDATES: ARRY-382 and ARRY-797 programs
Array is advancing a Phase 1/2 dose escalation immuno-oncology trial of ARRY-382 in combination with pembrolizumab (Keytruda), a PD-1 antibody, in patients with advanced solid tumors, including melanoma and non-small cell lung cancer. ARRY-382 is a wholly-owned, highly selective and potent, small molecule inhibitor of CSF-1R kinase activity.

Array plans to initiate a Phase 3 trial of ARRY-797, an oral, selective p38 MAPK inhibitor, in patients with LMNA A/C-related dilated cardiomyopathy later this year as it evaluates options regarding the asset, including advancing it internally, partnering the program for further development and commercialization or creating a separate company. LMNA A/C-related dilated cardiomyopathy is a rare, degenerative cardiovascular disease caused by mutations in the LMNA gene and characterized by poor prognosis.

OTHER BUSINESS DEVELOPMENT UPDATES
Selumetinib / MEK inhibitor (partnered with AstraZeneca)
In 2003, AstraZeneca acquired exclusive worldwide rights to selumetinib for oncology indications from Array. Under its agreement with AstraZeneca, Array has earned $26.5 million in up-front and milestone payments to date and has the potential to earn additional selumetinib milestone payments of approximately $30 million as well as royalties on product sales. On July 28, 2017, AstraZeneca and Merck announced an agreement to share the development and commercialization costs for selumetinib monotherapy and non-PD-L1/PD-1 combination therapy opportunities. Merck will fund all development and commercialization costs of Keytruda in combination with selumetinib. AstraZeneca will fund all development and commercialization costs of Imfinzi in combination with selumetinib. Under their agreement, gross profits from selumetinib product sales generated through monotherapy or combination therapies will be shared equally. AstraZeneca will book all product sales of selumetinib and gross profits due to Merck under the collaboration will be recorded by AstraZeneca under cost of sales. Based on this, Array remains eligible to receive from AstraZeneca milestones and royalties on all future selumetinib sales, and now expects to receive a portion of certain consideration paid by Merck to AstraZeneca. Array has informed AstraZeneca that it is disputing the small consideration that AstraZeneca intends to pay Array related to both upfront and potential future milestones under AstraZeneca’s agreement with Merck. Furthermore, prior to the announcement of the AstraZeneca / Merck agreement, Array informed AstraZeneca of its position that the Neurofibromatosis type 1 (NF1) development program is outside the permitted field of its license.

NEW PRECLINICAL LICENSE AND COLLABORATION AGREEMENT WITH AMGEN IN INFLAMMATION: Array to Advance Program for Autoimmune Disorders; Amgen Responsible for Clinical Development and Worldwide Commercialization
Array initiated a collaboration agreement with Amgen for the discovery and development of novel drugs for autoimmune disorders. The undisclosed target and lead inhibitors were discovered using Array’s proprietary Kinase-Directed Phenotypic Screening Platform that leverages Array’s deep expertise in chemistry and early lead development. Under the terms of the agreement, Amgen and Array will collaborate on preclinical development with Array leading the medicinal chemistry work. Amgen is responsible for clinical development and commercialization. In exchange for exclusive rights to Array’s preclinical program, Amgen will make upfront and milestone payments, as well as pay royalties on sales of resulting therapies.

FINANCIAL HIGHLIGHTS
Novartis continues to substantially fund all ongoing trials with binimetinib and encorafenib that were active or planned as of the close of the Novartis Agreements in 2015, including the COLUMBUS Phase 3 trial. Reimbursement revenue from Novartis was approximately $107 million for the previous 12 months, of which $22 million was recorded in the quarter ending June 30, 2017.

Fourth Quarter of Fiscal 2017 Compared to Third Quarter of Fiscal 2017 (Sequential Quarters Comparison)

Revenue for the fourth quarter of fiscal 2017 was $33.8 million, compared to $33.3 million for the prior quarter. Array achieved a $3 million milestone from Roche for advancement of ipatasertib, an AKT inhibitor, into a Phase 3 trial and a $1 million milestone from Loxo Oncology for advancement of LOXO-292, a RET inhibitor, into a Phase 1 trial.
Cost of partnered programs for the fourth quarter of fiscal 2017 was $10.1 million, compared to $7.4 million for the prior quarter. The increase was primarily due to higher costs incurred for the BEACON CRC trial as it continues to advance.
Research and development expense was $39.1 million, compared to $46.1 million in the prior quarter. The decrease was primarily due to reduced expenses associated with the Novartis transitioned studies.
Loss from Operations for the quarter was $26.3 million, which includes $3 million of stock-based compensation and $0.6 million of depreciation expense. This compares to a loss from operations of $31.9 million in the previous quarter, which included $2.9 million of stock-based compensation and $0.5 million of depreciation expense.
Net loss for the fourth quarter was $29.6 million, or ($0.17) per share, compared to $35.3 million, or ($0.21) per share, in the prior quarter. The decrease in net loss was primarily due to lower research and development expenses.
Cash, Cash Equivalents and Marketable Securities as of June 30, 2017 were $235.1 million.
Fourth Quarter of Fiscal 2017 Compared to Fourth Quarter of Fiscal 2016 (Prior Year Comparison)

Revenue for the fourth quarter of fiscal 2017 decreased $9.4 million compared to the same quarter of fiscal 2016. The decrease was primarily due to decreased reimbursement revenue for the Novartis transitioned studies.
Cost of partnered programs increased $4.6 million compared to the fourth quarter of fiscal 2016. The increase was primarily due to higher costs incurred for the BEACON CRC trial.
Research and development expense decreased $10.4 million, compared to the fourth quarter of fiscal 2016. The decrease was due to expenses associated with the Novartis transitioned studies.
Net loss for the fourth quarter of fiscal 2017 was $29.6 million, or ($0.17) per share, compared to $25.0 million, or ($0.17) per share, for the same quarter in fiscal 2016.
Full Year of Fiscal 2017 Compared to Full Year of Fiscal 2016 (Prior Year Comparison)

Revenue was $150.9 million for the fiscal year ended June 30, 2017, compared to $137.9 million in fiscal 2016. This increase was primarily driven by higher milestone revenue earned in 2017 from Loxo, Roche and Genetech.
Net loss for the fiscal year ended June 30, 2017, was $116.8 million, or ($0.72) per share, compared to a net loss of $92.8 million, or ($0.65) per share, in fiscal 2016. The increased loss was due to the higher spend on proprietary programs partially offset by higher milestone revenue.
Net cash used in operating activities for the fiscal year ended June 30, 2017 was $39 million, compared to $70 million in fiscal 2016. The lower cash used in 2017 was driven by receipt of a $31.2M upfront from our partner Ono.
CONFERENCE CALL INFORMATION
Array will hold a conference call on Wednesday, August 9, 2017 at 9:00 a.m. Eastern Time to discuss these results and provide an update on the progress of its key clinical development programs. Ron Squarer, Chief Executive Officer, will lead the call.

Date:
Wednesday, August 9, 2017
Time:
9:00 a.m. Eastern Time
Toll-Free:
(844) 464-3927
Toll:
(765) 507-2598
Pass Code:
44703107
Webcast, including Replay and Conference Call Slides: View Source

COLUMBUS Results

As presented at the 2016 Society for Melanoma Research Annual Congress, results from Part 1 of the COLUMBUS study showed that COMBO450 significantly extend PFS in patients with advanced BRAF-mutant melanoma, with a PFS of 14.9 months compared with 7.3 months observed with vemurafenib [hazard ratio (HR) 0.54, (95% CI 0.41-0.71, P<0.001)]. As part of the trial design, the primary analysis was based on a Blinded Independent Central Review (BICR) of patient scans, while results by local review at the investigative site were also analyzed. The table below outlines the median PFS (mPFS) results, as determined by both assessments, for COMBO450 versus vemurafenib, COMBO450 versus encorafenib, and encorafenib versus vemurafenib:



mPFS BICR

mPFS Local Review
COMBO450 vs. Vemurafenib

COMBO450
Vemurafenib

COMBO450
Vemurafenib

14.9 months
7.3 months

14.8 months
7.3 months

HR (95% CI): 0.54 (0.41-0.71); P<0.001

HR (95% CI): 0.49 (0.37-0.64); P<0.001

COMBO450 vs. Encorafenib

COMBO450
Encorafenib

COMBO450
Encorafenib

14.9 months
9.6 months

14.8 months
9.2 months

HR (95% CI): 0.75 (0.56-1.00); P=0.051

HR (95% CI): 0.68 (0.52-0.90); P=0.006

Encorafenib vs. Vemurafenib

Encorafenib
Vemurafenib

Encorafenib
Vemurafenib

9.6 months
7.3 months

9.2 months
7.3 months

HR (95% CI): 0.68 (0.52-0.90); P=0.007

HR (95% CI): 0.70 (0.54-0.91); P=0.008
In this study, COMBO450 was generally well-tolerated, with a median duration of treatment of 51 weeks and median relative dose intensity for encorafenib and binimetinib of 100% and 99.6%, respectively. Grade 3/4 adverse events (AEs) that occurred in more than 5% of patients receiving COMBO450 were increased gamma-glutamyltransferase (GGT) (9%), increased blood creatine phosphokinase (CK) (7%) and hypertension (6%). The incidence of selected any grade of AEs of special interest, defined based on toxicities commonly associated with commercially available MEK+BRAF-inhibitor treatments for patients receiving COMBO450 included: rash (23%), pyrexia (18%), retinal pigment epithelial detachment (13%) and photosensitivity (5%). Full safety results of COLUMBUS Part 1 were presented at the 2016 Society for Melanoma Research Annual Congress.

COLUMBUS Part 2 was designed specifically to assess the contribution of binimetinib to the combination of binimetinib and encorafenib by reducing the dose of encorafenib to 300mg in the combination arm to allow for a comparison of equal doses across arms. In COLUMBUS Part 2, the primary analysis compared PFS in patients treated with binimetinib 45mg twice daily plus encorafenib 300mg daily (COMBO300) to patients treated with encorafenib 300mg daily as a single agent. Top-line results showed the mPFS for patients treated with COMBO300 was 12.9 months compared to 9.2 months for patients treated with single agent encorafenib, with HR of 0.77 [95% CI 0.61-0.97, p=0.029]. COMBO300 was generally well-tolerated and reported dose intensity and AEs were consistent with COMBO450 results in COLUMBUS Part 1. Further results from COLUMBUS Part 2 will be presented at ESMO (Free ESMO Whitepaper) 2017.

Binimetinib and encorafenib are investigational medicines and are not currently approved in any country.

Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates[1-2]. There are about 200,000 new cases of melanoma diagnosed worldwide each year, approximately half of which have BRAF mutations, a key target in the treatment of metastatic melanoma[1, 3, 4].

About the Phase 3 COLUMBUS Study
The COLUMBUS trial, (NCT01909453), is a two-part, international, randomized, open label Phase 3 study evaluating the efficacy and safety of the combination of binimetinib plus encorafenib to vemurafenib and encorafenib monotherapy in 921 patients with locally advanced, unresectable or metastatic melanoma with BRAF V600 mutation. Prior immunotherapy treatment was allowed. Over 200 sites across North America, Europe, South America, Africa, Asia and Australia participated in the study. Patients were randomized into two parts:

In Part 1, 577 patients were randomized 1:1:1 to receive 45mg binimetinib plus 450mg encorafenib (COMBO450), 300mg encorafenib alone, or 960mg vemurafenib alone. The dose of encorafenib in the combination arm is 50% higher than the single agent maximum tolerated dose of 300mg. A higher dose of encorafenib was possible due to improved tolerability when combined with binimetinib. The primary endpoint for the COLUMBUS trial was a PFS comparison of COMBO450 versus vemurafenib. PFS is determined based on tumor assessment (RECIST version 1.1 criteria) by a Blinded Independent Central Review (BICR). Secondary endpoints include a comparison of the PFS of encorafenib monotherapy to that of COMBO450 and a comparison of overall survival (OS) for COMBO450 to that of vemurafenib alone.
In Part 2, 344 patients were randomized 3:1 to receive 45mg binimetinib plus 300mg encorafenib or 300mg encorafenib alone. Part 2 is designed to provide additional data to help evaluate the contribution of binimetinib to the combination of binimetinib and encorafenib. As the comparison of COMBO450 to encorafenib in Part 1 did not achieve statistical significance, analyses of other endpoints including the statistical analysis conducted in Part 2 is descriptive.

On August 9, 2017 Merrimack Pharmaceuticals, Inc. (NASDAQ: MACK) reported its second quarter 2017 financial results for the period ended June 30, 2017 (Press release, Merrimack, AUG 9, 2017, View Source [SID1234520083]).

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“This quarter’s progress, with key hires to the executive team and advancements in the clinic, has reinforced Merrimack’s refined corporate and clinical strategy. With a rich, biomarker-driven R&D pipeline, including data expected in 2018 for each of our lead assets – MM-121, MM-141 and MM-310 – and promising preclinical programs, we are well positioned to execute on our goals,” said Richard Peters, M.D., Ph.D., President and Chief Executive Officer.

Second Quarter and Recent Highlights

Key events from the second quarter and more recently include:

Expansion of Merrimack’s executive team with key appointments:
Dr. Sergio Santillana, a medical oncologist and former Chief Medical Officer at Ariad Pharmaceuticals with extensive industry experience leading a wide range of clinical development programs, as Chief Medical Officer;
Ellen Forest, an experienced human resources executive and former Director of Human Resources at Baxalta, as Head of Human Resources; and
Thomas Needham, a 25-year industry veteran, experienced dealmaker and former Senior Vice President of Business Development at C4 Therapeutics, as Chief Business Officer.
Completion of enrollment in the Phase 2 randomized, double-blind, placebo-controlled CARRIE study of MM-141 in combination with standard of care in previously untreated patients with metastatic pancreatic cancer who have high serum levels of free IGF-1. MM-141 is an inhibitor of the PI3K/AKT/mTOR signaling pathway, targeting the IGF-1 and HER3 receptors. Merrimack expects to report data in the first half of 2018.

Upcoming Milestones

Merrimack anticipates the following upcoming clinical milestones:

Initiation this year of the SHERBOC trial, a Phase 2 randomized, double-blind, placebo-controlled clinical study of MM-121 added to standard of care in patients with heregulin positive, hormone receptor positive, HER2 negative metastatic breast cancer;
Top-line results in the first half of 2018 from the Phase 2 randomized, double-blind, placebo-controlled CARRIE study of MM-141 in combination with standard of care in previously untreated patients with metastatic pancreatic cancer who have high serum levels of free IGF-1;
Top-line results in the second half of 2018 from the Phase 2 randomized SHERLOC study of MM-121 added to standard of care in patients with heregulin positive non-small cell lung cancer; and
Safety data and the recommended Phase 2 dose in the second half of 2018 from the Phase 1 clinical study of MM-310 in patients with solid tumors.

Second Quarter 2017 Financial Results

The following summarizes Merrimack’s financial results for the three months ended June 30, 2017:

In April, Merrimack received a $575.0 million upfront cash payment from Ipsen in connection with its asset sale, from which Merrimack fully paid off $175.0 million of outstanding Senior Secured Notes due in 2022; paid a special cash dividend of $140.0 million to stockholders in May; and invested approximately $125.0 million into the further development of its streamlined oncology pipeline;
Research and development expenses from continuing operations for the three months ended June 30, 2017 were $19.8 million, compared to $27.7 million for the three months ended June 30, 2016. This represents a decrease of $7.9 million primarily due to Merrimack’s transition to a refocused clinical and preclinical pipeline and offset by a one-time charge related to stock-based compensation;
General and administrative expenses from continuing operations for the three months ended June 30, 2017 were $14.8 million, compared to $8.1 million for the three months ended June 30, 2016. This represents an increase of $6.7 million, primarily due to costs associated with the transition following the asset sale, including legal expenses and stock-based compensation; and
Net loss attributable to Merrimack’s continuing operations for the three months ended June 30, 2017 was $28.9 million, or $0.22 per share, compared to a net loss attributable to Merrimack’s continuing operations of $51.4 million, or $0.41 per share, for the three months ended June 30, 2016.

Financial Outlook

Merrimack continues to believe that its unrestricted cash and cash equivalents of $135.5 million as of June 30, 2017, together with the potential net milestone payments anticipated from Shire, will be sufficient to fund its planned operations into the second half of 2019.