Kinase inhibitors in focus after Merck bid for ArQule

Merck’s $2.7B bid for ArQule is yet another example of Big Biopharma’s high regard for oral kinase inhibitors for treating cancer. ArQule’s lead drug is ARQ 531, an oral inhibitor of Bruton’s tyrosine kinase (BTK).

Previous deals include Pfizer’s (PFE -0.1%) $10.4B takeout of Array BioPharma and its lineup of tyrosine kinase inhibitors (TKIs), finalized in July, and Eli Lilly’s (LLY -0.2%) $8B acquisition of Loxo Oncology in February and its portfolio of RET, TRK and BTK inhibitor candidates and TRK inhibitor Vitrakvi (larotrectinib), approved in the U.S. in November 2018 for TRK fusion cancers.

AbbVie (ABBV -0.1%) bought Pharmacyclics for $21B in 2015 in order to secure the rights to BTK inhibitor Imbruvica (ibrutinib), sharing profits with Johnson & Johnson (JNJ +0.1%).

AstraZeneca (AZN +0.2%) acquired a majority stake in Acerta Pharma for $4B late 2015 for access to its kinase inhibitor lineup. Its first win was BTK inhibitor Calquence (acalabrutinib), approved in the U.S. in October 2017 for mantle cell lymphoma and last month for CLL.

Kinase inhibitor-related tickers: BeiGene (BGNE +0.6%), Principia  Biopharma (PRNB +3.5%), Merck KGaA (OTCPK:MKGAY), TG Therapeutics (TGTX +30.3%), Aptose Biosciences (APTO +37.9%), Exelixis (EXEL -1%), Deciphera Pharmaceuticals (DCPH +3.8%), Curis (CRIS -0.6%), Pulmatrix (PULM +1.1%), Verastem (VSTM +8.3%), BioCryst Pharmaceuticals (BCRX +0.2%), Aclaris Therapeutics (ACRS +6.6%), IDEAYA Biosciences (IDYA +1.8%), Rigel Pharmaceuticals (RIGL +1.4%), Astellas Pharma (OTCPK:ALPMY), Blueprint Medicines (BPMC -7.4%), Seattle Genetics (SGEN -2.7%), Spectrum Pharmaceuticals (SPPI +0.3%), Puma Biotechnology (PBYI -1%), Galapagos NV (GLPG +1.6%)

https://seekingalpha.com/news/3524810-kinase-inhibitors-in-focus-after-merck-bid-for-arqule

Aptose up 38% on encouraging CG-806 data

Thinly traded micro cap Aptose Biosciences (APTO +37.5%) is up on a 27x surge in volume in reaction to preclinical data on pipeline candidate CG-806. The results were presented at ASH in Orlando.

In CLL cells, CG-806 inhibited B-cell receptor signaling that led to CLL cell death and reduced proliferation with a greater effect than AbbVie’s Imbruvica (ibrutinib).

In mantle cell lymphoma cells, CG-806 showed superior anti-cancer action versus ibrutinib.

The company says CG-806 is an oral small molecule FLT3/BTK multi-cluster kinase inhibitor in development for blood cancers. It in-licensed the asset from South Korea’s CrystalGenomics in June 2018.

#ASH19

https://seekingalpha.com/news/3524875-aptose-up-38-on-encouraging-cgminus-806-data

SCOTUS rejects Arizona opioid case against Purdue Pharma & Sackler family

The U.S. Supreme Court has rejected a novel case brought by Arizona Attorney General Mark Brnovich aimed at recovering more money from privately held Purdue Pharma and the controlling Sackler family related to the company’s role in the opioid epidemic in the state.

Company lawyers argued that Arizona’s claims should be adjudicated in bankruptcy court, but Mr. Brnovich believed that the prominence of the U.S. opioid crisis justified the direct involvement of SCOTUS, a position supported by North Dakota, Ohio, Alaska, Louisiana and Utah.

The company and the Sacklers have proposed $10B and $3B, respectively, to settle all claims in the matter but half of the states have not signed on, believing that the settlement amounts should be higher.

Related tickers: Teva Pharmaceutical Industries (TEVA -0.3%), Johnson & Johnson (JNJ -0.1%), Mallinckrodt (MNK -2.1%), Endo International (ENDP -3.9%), McKesson (MCK +1.4%), Cardinal Health (CAH -0.5%), AmerisourceBergen (ABC -1%)

https://seekingalpha.com/news/3524866-scotus-rejects-arizona-opioid-case-against-purdue-pharma-sackler-family

Constellation Pharma Updates Prelim Data from MANIFEST Trial at ASH

• Preliminary data showed continuing signs of activity across a broad range of parameters, suggesting possible disease-modifying effects of CPI-0610
• In the first-line treatment arm, 12 out of 15 (80%) evaluable JAK-inhibitor-naïve patients treated with a CPI-0610 / ruxolitinib combination achieved at least a 35% spleen volume response (SVR35) at 12 weeks
• Clinical activity, including SVR35 responses, TSS50 responses, and conversion from transfusion dependence to transfusion independence, was seen at 24 weeks in patients in the second-line treatment arm who added CPI-0610 to ruxolitinib, suggesting that treatment with CPI-0610 may have durable effects
• An investor event to discuss the MANIFEST update at ASH is scheduled for 12:30 PM EST today

https://www.globenewswire.com/news-release/2019/12/09/1958004/0/en/Constellation-Pharmaceuticals-Provides-Updated-Preliminary-Data-from-MANIFEST-Clinical-Trial-with-CPI-0610-in-Oral-and-Poster-Presentations-at-ASH.html

Forty Seven Updates Data from Ongoing Trial of Magrolimab at ASH19

 Forty Seven Inc.  (NASDAQ:FTSV), a clinical-stage, immuno-oncology company focused on developing therapies to activate macrophages in the fight against cancer, today announced the presentation of updated clinical data from its ongoing trial evaluating magrolimab in combination with azacitidine for the treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The new results, which will be shared in an oral presentation at the 61^st American Society of Hematology (ASH) Annual Meeting in Orlando, Florida, show that the combination of magrolimab and azacitidine is highly active and well-tolerated in patients with MDS and AML.

“As a clinician caring for patients with MDS, I am reminded daily of the limitations of existing standard-of-care medicines, which are appropriate for a small fraction of people and leave nearly 75% receiving only supportive care or watchful waiting,” said David Sallman, M.D., H. Lee Moffitt Cancer Center and Research Institute, an investigator for the clinical trial. “The data that continue to emerge from this clinical trial are incredibly exciting, suggesting that the combination of magrolimab and azacitidine may offer the first new therapeutic regimen in over a decade, with the potential to induce meaningful and lasting responses in patients with higher-risk disease. Importantly, these results also support magrolimab’s tolerability profile, further differentiating it as a safe treatment that may be used even in more fragile, sicker, and older patients.”

“We are very encouraged by the tolerability and sustained clinical activity of the magrolimab and azacitidine combination observed thus far, which increase our confidence in the program and reinforce our commitment to advancing it as rapidly and as responsibly as possible,” said Chris Takimoto, M.D., Ph.D., F.A.C.P., Chief Medical Officer of Forty Seven. “To that end, we are pleased with our recent interactions with the U.S. Food and Drug Administration (FDA), and we appreciate the agency’s feedback as we finalized the design of our registration-enabling program.  With its guidance, we have developed a protocol that allows us two distinct opportunities to achieve an accelerated approval, while remaining on track to achieve our goal of filing an initial biologics license application (BLA) in the fourth quarter of 2021. We look forward to working with our investigators, clinicians and the broader patient community as we advance magrolimab forward for people living with MDS.”

https://www.biospace.com/article/releases/forty-seven-inc-announces-updated-data-from-ongoing-clinical-trial-of-magrolimab-showing-robust-durable-activity-in-patients-with-myelodysplastic-syndrome-and-acute-myeloid-leukemia/

Abeona Cleared to Initiate Pivotal Phase 3 Trial Evaluating EB-101 Gene Therapy

FDA removes clinical hold; Company may proceed with VIITAL™ study

Company expects to initiate study in the first quarter of 2020

Primary endpoint confirmed as proportion of wounds with greater than 50% healing at 3 months vs control wounds

Majority of potential subjects have been pre-screened for the study

Abeona Therapeutics Inc. (Nasdaq: ABEO), a fully-integrated leader in gene and cell therapy, today announced that the U.S. Food and Drug Administration (FDA) has removed its clinical hold and provided clearance to proceed with the VIITAL™ study, the Company’s pivotal Phase 3 clinical trial evaluating EB-101 for the treatment of recessive dystrophic epidermolysis bullosa (RDEB). The FDA removed the clinical hold following the Company’s submission of additional data points on transport stability of EB-101 to clinical sites. Abeona expects to initiate the VIITAL™ study in first quarter of 2020.

“The Abeona team has worked diligently to provide a prompt and thorough response to the FDA, enabling us to proceed with our pivotal Phase 3 trial for EB-101,” said João Siffert, M.D., Chief Executive Officer of Abeona. “Recently published long-term follow up data from our Phase 1/2 trial leaves us increasingly confident that EB-101 can provide durable healing for large, chronic wounds that afflict many RDEB patients. We are now focused on initiating the VIITAL™ study in the first quarter of 2020. The success in building and qualifying a state-of-the-art GMP manufacturing facility also represents a critical step toward bringing this novel product to patients in dire need of effective treatment.”

With two to five years of follow-up, data from a Phase 1/2 clinical trial conducted by Stanford University evaluating EB-101 showed that the gene-corrected cell therapy provided durable wound healing for RDEB patients, including for the largest, most challenging wounds that constitute the majority of wounds in this population.

https://www.biospace.com/article/releases/abeona-therapeutics-cleared-to-initiate-pivotal-phase-3-clinical-trial-evaluating-eb-101-gene-therapy-for-recessive-dystrophic-epidermolysis-bullosa/

Agios up on positive Tibsovo data

Agios Pharmaceuticals (NASDAQ:AGIO) is up 13% premarket on light volume in reaction to data on the combination of Tibsovo (ivosidenib) and chemo agent azacitidine (Celgene’s Vidaza) in IDH1 mutation-positive AML patients. The results were presented at ASH in Orlando.

Results from 23 newly diagnosed participants in a Phase 1/2 study showed a 61% (n=14) complete response (CR) rate, increasing to 70% (n=16) if CRs with partial hematologic recovery were included. Median duration of CR had not been reached at data cutoff.

#ASH19

https://seekingalpha.com/news/3524751-agios-up-13-premarket-positive-tibsovo-data