Miragen Therapeutics shares soar on leukemia data

Miragen Therapeutics announces data from Phase 1 trial of cobomarsen

Miragen Therapeutics (MGEN) announced new efficacy and safety data from the ATLL arm of its ongoing Phase 1 clinical trial of cobomarsen, which will be presented at the 12th Annual T-Cell Lymphoma Forum in La Jolla, CA, which is taking place from January 30th to February 1st.

Miragen shares soar on its test data, Stockwinners

Of note are the data from the subtype of aggressive ATLL patients (Adult T-Cell Leukemia Lymphoma (ATLL)) who at study entry had persistent residual disease after chemotherapy or other therapy.

In the trial, six patients of this subtype had an MST of 26 months with three patients still on treatment at the time of data analysis.

Adult T-Cell Leukemia Lymphoma does not have a cure, Stockwinners

The Company was most encouraged, however, by the observed biomarker activity showing that disease stabilization is marked by a decrease in biomarkers of tumor cells activation and proliferation, providing evidence of the biological mechanism effect of cobomarsen on disease stabilization.

The Company is evaluating cobomarsen in an ongoing Phase 1 basket trial of cancers where the disease process appears to be correlated with an increase in miR-155 levels, including ATLL, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia.

Today’s announcement includes results for the first 15 patients with aggressive subtypes of ATLL who were treated with three doses of cobomarsen by intravenous infusion, including 600, 900 and 1200 mg doses.

The preliminary results from this first-in-human Phase 1 clinical trial of the miR-155 inhibitor, cobomarsen, in patients with ATLL was observed to improve disease stabilization and reduce biomarker expression associated with ATLL cellular proliferation and activation in patients with persistent residual disease after chemotherapy and other therapies.

Of the 15 ATLL patients treated with cobomarsen, nine were actively relapsing at the time of screening, and six had residual nodal or circulating leukemic disease after chemotherapy or other systemic therapies.

For these six patients, the duration of cobomarsen treatment ranged from 4.5 to 23.7 months, with three patients still on study as of October 17, 2019.

MST of these patients was 26 months, compared with the 7.4 months MST from a retrospective external historical cohort based on a literature search of peer-reviewed papers. The Company compiled a historical external control which includes a series of studies with ATLL patients treated with standard of care over the past 10 years.

These studies included more than 6,000 ATLL patients. The Company calculated an MST from diagnosis of 7.4 months for patients with the aggressive ATLL subtypes, regardless of the type of therapy or number of therapies administered.

Five of these six patients treated with cobomarsen were alive as of the October 17, 2019 data analysis. In the trial, disease stabilization was marked by an observed decrease in Ki-67, a biomarker of cell proliferation, as well as other biomarkers of cell activation on circulating tumor cells, providing evidence of the biological mechanism effect of cobomarsen on disease stabilization.

For the clinical trial, the Company established a retrospective external historical cohort based on a literature search of peer-reviewed papers which reported MST from diagnosis and PFS on large cohorts of ATLL patients over the last decade.

A total of 16 papers describing unique cohorts of patients from Japan, the United States, South America and Europe were included in the MST retrospective analysis, of which 12 included data regarding MST for combined aggressive subtypes and eight reported MST for both acute and lymphomatous sub-types separately but not for the combined aggressive subtypes.

The number of patients included in each publication varied from 54 to 1,792, for a total of 6,440 patients.

Chronic administration of cobomarsen has been generally safe and well tolerated with a favorable safety profile over one year of dosing on a weekly basis.

There were 196 total reported adverse events as of October 17, 2019, with only 22% of the total AEs considered possibly related to study drug, and 86% of the total AEs considered mild or moderate. 14% of the total AEs were Grade 3 or 4 and most resolved within 11 days.

With no drug related deaths and only two serious adverse events occurring in the same patient and deemed possibly related to the study drug, the observed safety profile of cobomarsen in ATLL through October 17, 2019 appears to be benign and well tolerated with chronic dosing.

MGEN closed at $1.69, last traded at $2.80.

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Epizyme jumps on $100M investment

Royalty Pharma to purchase future royalties on tazemetostat from Eisai

Royalty Pharma announced that it has agreed to pay $330M to purchase Eisai Co.’s (ESALY) royalties on future worldwide sales of tazemetostat, Epizyme’s (EPZM) lead investigational agent, outside of Japan, and made an equity investment in Epizyme of $100M, with options to invest up to an additional $100M in Epizyme common stock.

In addition, investment funds managed by Pharmakon Advisors agreed to provide $70M in senior-secured loans with the possibility to fund up to $370M over time.

Tazemetostat is a first-in-class, oral EZH2 inhibitor in clinical development for certain oncology indications, including epithelioid sarcoma and follicular lymphoma.

Epizyme receives a $100M investment, Stockwinners

Under a collaboration agreement between Epizyme and Eisai, Epizyme is responsible for the development and worldwide commercialization of tazemetostat (outside of Japan) and Eisai is responsible for the development and commercialization of tazemetostat in Japan.

As part of the agreement, Epizyme owes milestones and royalties on sales of tazemetostat outside of Japan to Eisai, and Eisai owes royalties on sales of tazemetostat in Japan to Epizyme.

Under the terms of its agreement with Eisai, Royalty Pharma has acquired Eisai’s future worldwide royalties on net sales by Epizyme of tazemetostat outside of Japan, for an upfront payment of $110M plus up to an additional $220M for the remainder of the royalty upon FDA approval of tazemetostat for certain indications.

Under the terms of its agreement with Epizyme, Royalty Pharma will make an upfront payment of $100M for shares of Epizyme common stock based on a price of $15 per share.

Royalty Pharma makes $100M investment in Epizyme, Stockwinners

Epizyme has an 18-month option to sell an additional $50M of its common stock to Royalty Pharma at then prevailing prices, not to exceed $20 per share, and Royalty Pharma has a three-year option to purchase an additional 2.5M shares of Epizyme common stock at $20 per share.

In addition, Royalty Pharma will make additional payments to Epizyme if annual net sales of tazemetostat outside of Japan exceed certain thresholds, and Epizyme has assigned to Royalty Pharma the future royalty streams on tazemetostat sales in Japan previously owed to Epizyme by Eisai.

Epizyme has also agreed to appoint a representative from Royalty Pharma to its board of directors. Under the terms of the loan agreement with Epizyme, investment funds managed by Pharmakon Advisors will fund $25M at closing and up to an additional $45M in two tranches.

In addition, the loan agreement contemplates the potential for an additional $300M, subject to mutual agreement of the parties. The loans will have a coupon of LIBOR + 7.75% and a 5-year maturity.

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Aveo Pharma. shares tumble following FDA meeting

Aveo Pharmaceuticals provides update after FDA meeting discussing TIVO-3 results

Aveo Pharmaceuticals (AVEO) provided a regulatory update following a meeting with the FDA to discuss results from the August overall survival, or OS, analysis of the TIVO-3 trial and the company’s proposal to proceed with a new drug application, or NDA, for tivozanib. TIVO-3 is the company’s Phase 3 randomized, controlled, multi-center, open-label study to compare tivozanib, the company’s vascular endothelial growth factor receptor tyrosine kinase inhibitor, or VEGFR-TKI, to sorafenib in 350 subjects with highly refractory metastatic renal cell carcinoma, or RCC.

AVEO shares tumble following FDA meeting, Stockwinners

The TIVO-3 trial was designed to address the FDA’s concerns regarding the OS trend in the TIVO-1 trial. In the TIVO-1 trial, the company’s initial RCC pivotal trial, the FDA found that the inconsistent progression free survival, or PFS, and OS results and imbalance in post study treatments made the trial results uninterpretable and inconclusive when making a risk-benefit assessment necessary for drug approval.

The company previously announced that the TIVO-3 trial met its primary endpoint of demonstrating a significant improvement in PFS. The study also demonstrated a significant improvement in the secondary endpoint of overall response rate.

The August analysis of the secondary endpoint of OS was the second prespecified interim OS analysis of the TIVO-3 trial, and showed an updated OS hazard ratio, or HR, of 0.99 at two years from the last patient enrolled in the study.

In the FDA’s preliminary feedback, based on its assessment of the totality of evidence presented to date, the FDA recommended that the company not submit an NDA at this time.

The FDA stated that it remained concerned about the results of TIVO-3 in the context of the overall development of tivozanib. The FDA noted that the company’s current interim OS results do not abrogate the FDA’s concerns over detriment and that those results may worsen with final analysis at 263 events and that the median OS for tivozanib is worse than that of sorafenib.

In view of the changing first-line treatment landscape as well as the FDA’s continued concerns, the company informed the FDA that it intends to narrow its proposed indication to relapsed/refractory RCC.

At the meeting, the FDA acknowledged AVEO’s responses and reiterated its concerns about the survival information and the totality of data.

The FDA noted that the choice to submit the data is the company’s, and that a discussion with the Oncologic Drug Advisory Committee will likely be required.

The FDA said that if AVEO wishes to proceed with a revised OS analysis in June 2020, AVEO should submit an updated statistical analysis plan, or SAP, with a planned OS update based on the projected number of events at that time.

AVEO intends to submit to the FDA an update to the SAP for the final OS analysis consistent with these discussions, followed by an NDA submission in Q1 of 2020.

AVEO expects to report the final OS analysis in June 2020 based on a May 1, 2020 cutoff, at which point the company estimates that the study will have reached approximately 263 OS events, as discussed with the FDA.

The FDA and the company agreed that if the final analysis yields an OS HR above 1.00, the company will withdraw its NDA application.

AVEO shares are down 35% to $0.59.

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Bempegaldesleukin data should send Nektar shares higher

Nektar presents biomarker, clinical data from PIVOT-02 Phase 2 study

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Nektar presents biomarker, clinical data from PIVOT-02 Phase 2 study, Stockwinners

Nektar Therapeutics (NKTR) announced that biomarker and clinical data from PIVOT-02 was presented at the 2019 American Society of Clinical Oncology Meeting in Chicago, Illinois.

#Bempegaldesleukin is an investigational, CD122-preferential IL-2 pathway agonist designed to provide sustained signaling through the IL-2 beta-gamma receptor.

Bempegaldesleukin is under investigation in clinical trial NCT03729245 (A Study of NKTR-214 in Combination With Nivolumab Compared With the Investigator’s Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC)).

PIVOT-02 is an ongoing Phase 2 study evaluating bempeg in combination with nivolumab in solid tumors.

Exploratory biomarker analyses of PIVOT-02 baseline tumor biopsies identified immune signatures that potentially enrich for response in patients with 1L metastatic melanoma and not 1L metastatic urothelial carcinoma.

Notable response rates were seen in both 1L metastatic melanoma and 1L metastatic urothelial cancer patients, regardless of PD-L1 status or unfavorable tumor microenvironments.

At a median time of follow-up of 12.7 months, confirmed objective response rate was 53% in efficacy-evaluable patients, with 34% of patients achieving confirmed complete responses. 42% of patients achieved a maximum reduction of 100% in target lesions. DCR, also known as disease control rate was 74%.

Median time to response was 2 months. Median duration of response was not reached. At the 12.7 month median follow-up, data were too immature to calculate median progression-free survival. 80% of patients with responses have ongoing responses. Amongst the 35 patients with known pre-treatment PD-L1 status, ORR in PD-L1 negative patients was 6/14 and in PD-L1 positive patients was 13/21.

One of three patients with unknown PD-L1 baseline status experienced a CR.

A total of 6/41 of patients experienced a Grade 3 or higher TRAE with 4/41 patients discontinuing treatment due to a TRAE. A total of 41 patients have been treated at the RP2D with 3 patients discontinuing prior to 1st scan due to an unrelated treatment-emergent adverse event and patient decision.

A Phase 3 trial evaluating bempeg in combination with nivolumab versus nivolumab in first-line advanced melanoma patients is currently recruiting patients.

A Phase 2 pivotal trial evaluating bempeg in combination with nivolumab in first-line metastatic urothelial cancer is currently recruiting patients.

 Piper Jaffray

Piper Jaffray analyst Tyler Van Buren reiterates an Overweight rating and $100 price target on Nektar, and believes shares should be up significantly on Monday following updated data from the bempegaldesleukin + nivo PIVOT-02 melanoma cohort.

The increase in complete response rate from 24% to 34% at just beyond 12 months is more than the analyst and investors were anticipating and “the waterfall plot is like nothing [he has] ever seen in solid tumors.”

Ultimately, Van Buren believes the high quality of responses and the ability to maintain patients on therapy is contributing to robust durability, which increases his confidence in the ultimate outcome of the Phase III trial which will have a final mPFS evaluation around Q3 of 2020.

NKTR closed at $31.32.

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Cara Therapeutics shares jump on KALM-1 data

Cara Therapeutics announces topline data from KALM-1 Phase 3 trial

Cara reports positive top-line data from CR845, Stockwinners
Cara reports positive results from the KALM-1 pivotal Phase 3 trial of Korsuva Injection in hemodialysis patients , Stockwinners

Cara Therapeutics (CARA) announced topline data from the KALM-1 pivotal Phase 3 trial of Korsuva Injection in hemodialysis patients with moderate-to-severe chronic kidney disease-associated pruritus, or CKD-aP.

Chronic kidney disease-associated pruritus ( #CKD-aP ) is a distressing, often overlooked condition in patients with CKD and end-stage renal disease. It affects ~40% of patients with end-stage renal disease and has been associated with poor quality of life, poor sleep, depression, and mortality.  Despite being an annoyance, CKD-associated pruritus (CKD-aP) can adversely affect the quality of life (QOL) and medical outcomes. 

The proportion of patients on 0.5 mcg/kg of Korsuva Injection achieving a three-point or greater improvement from baseline in the weekly mean of the daily 24 hour Worst Itching Intensity Numeric Rating Scale, or WI-NRS, score at week 12 was 51% vs. 28% for patients on placebo.

The proportion of patients on 0.5 mcg/kg of Korsuva Injection achieving a four-point or greater improvement from baseline in the weekly mean of the daily 24 hour WI-NRS score at week 12 was 39% vs. 18% for patients on placebo.

Patients on #Korsuva Injection experienced a 43% improvement in the average total Skindex-10 score at week 12 vs. patients on placebo.

Patients on Korsuva Injection experienced a 35% improvement in the average total 5-D Itch score at week 12 vs. patients on placebo.

Korsuva was generally well-tolerated with a safety profile consistent with that seen in earlier Korsuva clinical trials.

Overall, the incidence of adverse events, or AEs, and serious AEs were similar across both Korsuva and placebo groups.

The most common treatment emergent AEs reported in greater than 5% of patients were diarrhea, dizziness, nasopharyngitis and vomiting.

CARA is up 12.5% to $20.21 per share.

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Merck reports positive results of its renal cell carcinoma drug

Merck presents results from Phase 3 KEYNOTE-426 study

Merck presents results from Phase 3 KEYNOTE-426 study, Stockwinners
Merck presents results from Phase 3 KEYNOTE-426 study, Stockwinners

Merck (MRK) announced presentation of the full results from the pivotal Phase 3 KEYNOTE-426 trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with Pfizer’s (PFE) Inlyta, a tyrosine kinase inhibitor, for the first-line treatment of advanced renal cell carcinoma at the 2019 Genitourinary Cancers Symposium.

Merck's anti-PD-1 therapy works in combination with Pfizer's (PFE) Inlyta, Stockwinners

Merck’s anti-PD-1 therapy works in combination with Pfizer’s (PFE) Inlyta

This is the first combination regimen to significantly improve overall survival, progression-free survival and objective response rate compared to sunitinib.

Results were consistent across all IMDC subgroups, including favorable, intermediate and poor risk groups, and regardless of PD-L1 expression.

As previously announced, the U.S. Food and Drug Administration has granted priority review for a supplemental Biologics License Application for #KEYTRUDA in combination with axitinib for the first-line treatment of patients with advanced RCC based on the results of KEYNOTE-426, and has set a Prescription Drug User Fee Act, or target action, date of June 20, 2019.

Findings from the first interim analysis showed KEYTRUDA in combination with axitinib reduced the risk of death by 47% – significantly improving OS compared to sunitinib.

For the dual primary endpoint of PFS, the KEYTRUDA combination showed a reduction in the risk of progression of disease or death of 31% compared to sunitinib.

In the study, the ORR was 59.3% for patients who received KEYTRUDA in combination with axitinib and 35.7% for those who received sunitinib, with a complete response rate of 5.8% and 1.9% and a partial response rate of 53.5% and 33.8%, for patients receiving the KEYTRUDA combination or sunitinib, respectively.

Median duration of response was not reached in the KEYTRUDA combination arm and was 15.2 months in the sunitinib arm. The results for OS, PFS and ORR were consistent across all IMDC risk groups and seen regardless of PD-L1 expression.

The observed adverse event profile was as expected based on the known profiles of KEYTRUDA and axitinib.

There was a higher incidence of grade 3 or 4 liver enzyme elevation with KEYTRUDA plus axitinib than previously observed with each agent as monotherapy.

Merck has filed these data with regulatory authorities worldwide.

Merck has an extensive clinical development program in RCC and is advancing multiple potential registration-enabling studies with KEYTRUDA, as monotherapy and in combination with other treatments, including KEYNOTE-564 and KEYNOTE-581.

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