AutoGenomics system to ID opioid dependency risk a breakthrough: FDA

AutoGenomics, Inc., based in Carlsbad, CA, announced that its INFINITI® Neural Response Panel has been granted designation as a Breakthrough Device by the US Food and Drug Administration (FDA).

The INFINITI® Neural Response Panel is a qualitative in vitro diagnostic test for the identification of patients who may be at risk for opioid dependency. The Panel is designed to identify 16 genetic mutations involved in the brain reward pathways that are associated with increased risk of opioid use disorder, and is intended for use by physicians as an aid for safe and effective pain management.

The Breakthrough Device Program is reserved for certain medical devices that demonstrate the potential to address unmet medical needs. The program is intended to help patients have more timely access to devices and breakthrough technologies that more effectively diagnose or treat life-threatening or irreversibly debilitating diseases or conditions. Under the Breakthrough Device Program, the FDA will provide its support to advance the INFINITI® Neural Response Panel. The commitment from the FDA for priority and expedited review and senior management involvement will enable a reduced regulatory timeline.

Addiction is a chronic, relapsing brain disease that is characterized by compulsive drug use despite harmful consequences. According to a Columbia University study, 40 million Americans age 12 and over meet the clinical criteria for addiction involving nicotine, alcohol or other drugs. Opioid drugs play an important role in the clinical management of pain despite a broad spectrum of side-effects that induce a sense of euphoria often leading to addiction. According to the Center for Disease Control and Prevention (CDC), more than 64,000 deaths were the result of drug overdose in the US in 2016. The surge in prescription and illicit opioid abuse is likely the main driver of this trend.

According to the American Society of Addictive Medicine (ASAM) and NIDA, up to 60% of substance abuse is due to genetic factors, that is not routinely tested since there is no commercially available diagnostic test that would identify a patient’s genetic risk of opioid dependency. AutoGenomics conducted extensive research in the scientific literature of addiction studies that led to the development of the INFINITI® Neural Response Panel. These findings were first presented at the 69^th AACC Annual Scientific Meeting & Clinical Lab Expo in San Diego in July 2017. AutoGenomics received the 2017 Industry Division Poster Award for its research entitled “Risk assessment of opioid addiction with a multi-variant genetic panel involved in the brain reward pathway,“ which describes the predictive algorithm of the Panel

“We believe that this multi-variant addiction panel with its predictive algorithm represents a significant tool for healthcare practitioners to identify and better manage patients at risk of opioid dependency,” said Fareed Kureshy, President and Chief Executive Officer of AutoGenomics.

AutoGenomics has notified the FDA of its intent to pursue premarket clearance through the FDA De Novo process.

https://bit.ly/2sB23Qr

Translate files for $115M IPO to trial ex-Shire mRNA cystic fibrosis treatment

Translate Bio has filed to raise $115 million from public investors. The IPO will tee Translate up to trial an mRNA candidate designed to enable all cystic fibrosis patients to produce fully functional CTFR proteins.

Lexington, Massachusetts-based Translate is built upon an mRNA therapeutic platform it bought from Shire late in 2016. The deal transferred the platform, its scientific founders and product candidates to Translate, which has since progressed the most advanced asset into the clinic. That done, Translate is seeking $115 million to fund clinical trials in cystic fibrosis and OTC deficiency.

Having been held up by a CMC-related clinical hold, Translate began a phase 1/2 trial of MRT5005 in cystic fibrosis last month. The study will enroll 32 patients and randomize them to receive either its mRNA therapy or placebo. Translate is looking to the trial for evidence of the safety of MRT5005 and its ability to deliver mRNA to epithelial cells.

The asset consists of an mRNA sequence packaged in a lipid-based nanoparticle. The size and lipid composition of the nanoparticles are designed to enable them to get mRNA into lung cells when delivered via a nebulizer. Preclinical studies suggest the drug is suitable for repeat dosing, an important consideration given the turnover of epithelial lung cells.

Translate is some way off from generating clinical data to support the idea, with the multiple ascending dose stage of the blinded study still months away from starting. But, having dosed one patient in the single ascending dose stage, Translate already has a safety signal serious enough to warrant bringing up in its IPO filing.

The patient developed transient, flulike symptoms that responded to treatment. As the trial is blinded, Translate has yet to learn whether the patient is on MRT5005, but other studies of nebulized nanoparticles have reported similar symptoms.

Translate, formerly known as RaNA Therapeutics, had expected to be in the clinic last year but took a detour. In 2015, RaNA raised $55 million, setting it up to move oligonucleotide treatments for spinal muscular atrophy and Friedreich’s ataxia into human testing starting in 2017.

RaNA pivoted away from the plan 12 months ago when it decided to dial down its oligonucleotide work and make the platform it bought from Shire its top priority. By the first quarter of 2018, spending on oligonucleotides had fallen to $69,000. The cystic fibrosis program went through more than $4 million over the same period.

The preclinical pivot has contributed to Translate chewing through $170 million to date. As RaNA, the biotech received money from Atlas Venture Fund and GlaxoSmithKline’s and Merck’s VC wings, among others. The three funds each own more than 5% of Translate. Shire owns almost 20% of the biotech and, under the terms of its contract with Translate, is set to add to its holdings through the IPO.

https://bit.ly/2sD5G7y

#ASCO18: Deciphera has positive interim Phase 1 data, updates

Deciphera Pharmaceuticals, Inc. (NASDAQ: DCPH) announced the presentation today of updated data from its ongoing Phase 1 clinical trial of DCC-2618, the company’s broad-spectrum KIT and PDGFRα inhibitor, in patients with gastrointestinal stromal tumors (GIST) at the American Society of Clinical Oncology (ASCO) Annual Meeting 2018, in Chicago, Illinois and provided additional clinical and regulatory updates on DCC-2618.

Suzanne George, M.D. Assistant Professor of Medicine, Harvard Medical School and Clinical Director, Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute presented the poster titled “Mutational Profile of Drug Resistant GIST Patients Enrolled in the Phase 1 Study of DCC-2618”. In addition to describing the mutational profile of KIT in GIST patients, the poster includes details of locally-read Objective Response Rates (ORR) and Disease Control Rates (DCR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) in second, third, and fourth and fourth line plus GIST patients that received DCC-2618 at doses of ≥100mg daily for at least one 28-day cycle prior to February 2, 2018:

Line of Therapy		GIST Patients (n)		DCR at 3 Months		ORR
2nd Line1		25		79%		24%
3rd Line1		29		82%		24%
≥4th Line		91		64%		9%
Total		145		70%		15%

1 46 of 54 second and third line patients received 150mg once daily dose.

The combined 24% ORR and 80% 3-month DCR in second and third line patients receiving DCC-2618 at doses of ≥100mg per day exceeds previously published results of registrational trials for the currently approved therapies for second line (sunitinib) and third line (regorafenib), which have reported ORRs of 7.0% and 4.5%, respectively, and levels of disease control of 60% and 53%, respectively.

“The preliminary data presented today on DCC-2618’s activity in second and third line GIST patients is very encouraging and supports the planned initiation later this year of our Phase 3 trial, INTRIGUE, in second line GIST patients,” said Michael D. Taylor, Ph.D., President and Chief Executive Officer of Deciphera. “The mutational profiling data across second, third and fourth line GIST patients observed in the Phase 1 study also demonstrates the need for the broadest spectrum of KIT inhibition in all GIST patients who previously received imatinib.”

“We are very pleased with the results presented today demonstrating DCC-2618’s potential to provide improved clinical benefit for not only heavily pre-treated patients, but also for second and third line GIST patients,” said Oliver Rosen, M.D. Chief Medical Officer of Deciphera. “Combined with the tolerability data presented at AACR in April 2018, these results demonstrate the potential of DCC-2618 as an effective and well tolerated therapy for a wide range of GIST patients.”

Highlights from the poster presentation include:

• Initial Objective Response Rates and Disease Control Rates with DCC-2618 at Doses of ≥100mg Daily in Second and Third Line GIST Patients Exceed Previously Published Results of Registrational Trials for Currently Approved Therapies, as well as the Results Observed in Heavily Pre-Treated GIST Patients Receiving DCC-2618:
  • 24% ORR with DCC-2618 observed to date in second and third line GIST patients is higher than that reported for sunitinib in second line patients (7.0%) or regorafenib in third line patients (4.5%).
  • These interim results show improved ORR and 3-month DCR in second line GIST patients treated with DCC-2618 compared to fourth and fourth line plus GIST patients treated with DCC-2618.
• Mutational Profiling Data Across Second, Third and Fourth Line GIST Patients Demonstrates the Breadth of KIT Mutations in GIST and the Ability of DCC-2618 to Reduce KIT Mutant Allele Frequency (MAF):
  • Resistance mutations in KIT in exons 13, 14, 17 and 18, or a combination thereof, occurs in second, third and, fourth and fourth line plus patients.
  • The KIT mutational profile in both tumors and plasma at baseline in GIST patient supports the need for a broad-spectrum KIT inhibitor in all post-imatinib lines of therapy.
  • 57 of 73 patients (78%) receiving DCC-2618 at doses of ≥100 mg daily demonstrated reductions in KIT MAF of more than 50%.

In addition, the company is providing the following clinical and regulatory updates on DCC-2618:

• Planned Initiation of a Phase 3 Trial in Second Line GIST Patients in 2018
  • Preliminary efficacy results in second line patients together with recently presented tolerability data at the recommended phase 2 dose (RP2D) of 150mg QD support the planned, randomized Phase 3 trial, INTRIGUE, in second line GIST.
  • Following discussions with regulatory authorities in the United States and in Europe, the company has designed INTRIGUE as a randomized, multicenter, open-label, Phase 3 trial in second line GIST. This registration study is expected to enroll approximately 350 patients who will be randomized 1:1 to either DCC-2618 or sunitinib, the current standard of care in second line; with median progression free survival as the primary endpoint.

• Interim Results with DCC-2618 at Doses of ≥100mg Daily Demonstrate Robust Clinical Activity in Heavily Pretreated GIST Patients, Including Patients Previously Treated with the Investigational Agent avapritinib (BLU-285):
  • 10 patients with KIT-driven GIST who previously received avapritinib were enrolled and treated with DCC-2618 as of January 31, 2018.
  • 6 out of 10 (60%) of these patients achieved stable disease as best response by RECIST during treatment with DCC-2618. In addition, one patient achieved stable disease following intra-patient dose escalation to 150mg BID.
  • 5 out of 10 (50%) of these patients were on study as of April 18, 2018.
  • 3 out of 10 (30%) of these patients received DCC-2618 for more than six months. Two of these patients achieved continued stable disease and remain on study as of April 18, 2018. The third patient with progressive disease was dose escalated and was reported as off study as of April 18, 2018.

A copy of the poster presentation will be available on the Science section of the Deciphera website under “Presentations and Publications” at http://www.deciphera.com.

https://bit.ly/2JbWbmK

Amphastar gets FDA OK to produce heparin in China unit

Amphastar announced that the U.S.FDA granted approval of the company’s abbreviated new drug application supplement for the manufacture of semi-purified heparin at the company’s subsidiary, Amphastar Nanjing Pharmaceuticals and the manufacture of heparin sodium USP at the company’s subsidiary, International Medication Systems, Limited.

https://bit.ly/2Hmaa80

Evelo started at buy by Cowen

Evelo Biosciences initiated with an Outperform at Cowen. Cowen analyst Chris Shibutani initiated Evelo Biosciences with an Outperform rating as he believes its innovate monoclonal microbials have the potential to emerge as a a novel class of medicines for unmet needs in a range of serious diseases

https://bit.ly/2LibF9C

#ASCO18: Array extended survival time for melanoma med in ‘Best in ASCO’

Array BioPharma announced updated results from the Phase 3 COLUMBUS trial in BRAF-mutant advanced melanoma. The results showed median overall survival was 33.6 months for patients treated with the combination of encorafenib and binimetinib compared to 16.9 months for patients treated with vemurafenib as a monotherapy. The combination reduced the risk of death compared to treatment with vemurafenib alone. The observed efficacy of vemurafenib in the control arm is also consistent with historical data, providing an additional benchmark for validating the patient population and results observed in COLUMBUS. Further, the two-year OS with combination therapy was 58%. These results will be part of an oral presentation at the American Society of Clinical Oncology annual meeting in Chicago, Illinois and have been selected for the “Best of ASCO” program

https://bit.ly/2LigRKy

Retrophin can proceed with Phase 3 of neural pediatric med: panel

Retrophin announced that the independent Data Monitoring Committee for the pivotal Phase 3 FORT Study, which is evaluating fosmetpantotenate for the treatment of pantothenate kinase-associated neurodegeneration, has completed its scheduled clinical safety review required to open enrollment for pediatric patients. Upon review of the available safety and tolerability data of fosmetpantotenate in adult patients with PKAN in the study to date, the DMC recommended that the pivotal trial continue as planned, and supported initiation of enrollment in pediatric patients aged 6 to 17. The FORT Study is a pivotal Phase 3 clinical trial conducted under a Special Protocol Assessment agreement with the U.S. Food and Drug Administration. Under the terms of the SPA agreement, the FORT Study protocol required an initial group of adult patients be treated with fosmetpantotenate to allow a safety assessment by the DMC prior to opening enrollment to pediatric patients aged 6 to 17. The Company anticipates completion of patient enrollment around year-end 2018, and top-line data to become available in the second half of 2019.

https://bit.ly/2J9DcNT