#ASCO18: Fabre, Idera, Kyowa Kirin, Portola

There’s plenty of news coming out of the American Society of Clinical Oncology (ASCO)Annual Meeting behind held in Chicago. Here’s a look at a few more of the top stories.

Pierre Fabre and Array BioPharma Update Phase III Melanoma Trial Data

The two companies announced results from the Phase III COLUMBUS trial in BRAF-mutant advanced melanoma. The median overall survival (mOS) was 33.6 months for patients receiving the combination of encorafenib and binimetinib compared to 16.9 months for patients receiving vemurafenib as a monotherapy. The combination also reduced the risk of death compared to vemurafenib monotherapy. The two-year OS with the combination was 58 percent.

Idera Pharmaceuticals’ ILLUMINATE-204 Trial Looks Good in Melanoma

Idera Pharma presented results from its ongoing ILLUMINATE-204 clinical trial of tilsotolimod, its intratumorally-delivered Toll-like Receptor (TLR) 9 agonist in combination with Yervoy (ipilimumab). The data showed an overall response rate (ORR) of 38 percent for the combination, including two complete responses and an ongoing partial response (PR) for 12 months. “We have clinical evidence that tilsotolimod activates both the innate and adaptive immune responses, and when used in combination with a checkpoint inhibitor like ipilimumab, triggers immune responses in previously resistant tumors,” said Adi Diab, lead trial investigator, assistant professor, Department of Melanoma Medical Oncology for University of Texas, MD Anderson Cancer Center, in a statement. “In patients with metastatic melanoma receiving premborlizumab who switched to single agent tipilimumab at the time of disease progression the reported ORR was 13 percent. The ORR was 38 percent observed in the ILLUMINATE-204 study and the duration of response, which is ongoing in most of the responders, is particularly encouraging and suggests that the combination of tilsotolimod and ipilimumab is a very promising strategy for treating patients with metastatic melanoma whose cancer does not respond to PD-1 therapy alone.”

Kyowa Kirin’s Mogamulizumab has Positive Progression Free Survival in Mycosis Fungoides

Tokyo’s Kyowa Hakko Kirin presented additional data from the pivotal MAVORIC trial. The Phase III trial evaluated mogamulizumab versus vorinostat to treat adults with relapsed or refractory mycosis fungoides (MF) or Sezary syndrome (SS) after at least one prior systemic therapy. MF and SS are the most common subtypes of cutaneous T-cell lymphoma (CTCL). The primary endpoint was PFS, which had a clinically relevant and statistically significant increase over vorinostat.

Portola Pharmaceuticals’ SYK-JAK Inhibitor Shows Efficacy in Pre-Treated B- and T-Cell Cancers

Portola Pharma announced new interim results from its ongoing Phase IIa trial of cerdulatinib, an oral SYK/JAK inhibitor, in patients with specific subtypes of B and T-cell Non-Hodgkin Lymphoma (NHL), including relapsed/refractory follicular lymphoma (FL) and peripheral T-cell lymphoma (PTCL), and chronic lymphocytic lymphoma/small lymphocytic lymphoma (CLL/SLL). Seven of the 20 patients in the PTCL cohort had a complete response. “Cerdulatinib continues to demonstrate promising results across a wide range of B- and T-cell malignancies, including early indications of the potential for durable responses,” said Paul Hamlin, medical director for the David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center, in a statement. “The new signals in relapsed/refractory PTCL and CTCL are particularly compelling when you consider the limited treatment options for patients that fail front-line therapy.”

Agios Pharmaceuticals’ Invosidenib in Early Trial in Acute Myeloid Leukemia Looks Promising

Agios Pharma presented data from a Phase I trial looking at ivosidenib (AG-120) or enasidenib (AG-221) in combination with azacitidine in newly diagnosed isocitrate dehydrogenase (IDH) mutant acute myeloid leukemia (AML). “Patients with newly diagnosed AML who are ineligible for intensive ‘7+3’ chemotherapy typically have poor outcomes and few available treatment options,” said Courtney DiNardo, lead investigator and assistant professor, department of leukemia at the University of Texas MD Anderson Cancer Center, in a statement “With additional patients now treated in the ivosidenib arm of this Phase I study, the updated combination data demonstrate a favorable safety profile and impressive response rates versus those expected with azacitidine alone. I look forward to further demonstrating the clinical benefit of utilizing an IDH inhibitor in combination with traditional frontline AML treatment as part of the ongoing Phase I and randomized trials.”

https://bit.ly/2xHpdJJ

#ASCO18: Genomic Health Up As TAILORx Data Clarifies Oncotype DX Utility

Genomic Health’s stock skyrocketed Monday on the news of a study in the New England Journal of Medicine that finally answered the question of how doctors should interpret and act upon an intermediate result from the firm’s Oncotype DX breast cancer risk test.

The company’s stock rose nearly 20 percent to $47.49 in afternoon trading on the Nasdaq.

The data, which was also presented over the weekend at the American Society for Clinical Oncology annual meeting in Chicago, showed that women with Oncotype DX recurrence scores from a low-risk threshold of 11 up to a high-risk threshold of 25 appear to benefit equally when treated with endocrine therapy alone compared to hormonal therapy with added chemotherapy, as long as they are over 50 years of age. Though doctors had known from previous studies that a low-risk score could be prognostic and a high-risk score could be predictive, the intermediate scores were trickier to interpret.

Researchers presenting the study estimated that the new classification architecture means that the percentage of individuals with early-stage hormone-receptor positive, HER-2 negative tumors who can confidently avoid chemo is about 70 percent overall.

In a note to investors on Sunday evening, Canaccord Genuity analyst Mark Massaro reiterated his Buy rating for Genomic Health and raised his price target on the firm’s stock to $45 from $41, noting that the TAILORx data “is at least ‘good enough’ to drive some incremental boost to Oncotype DX volumes globally, and perhaps more obviously, turn on reimbursement where coverage is limited (particularly in Germany).”

Genomic Health’s management believes that capitalizing on the TAILORx data can help the firm hit the high end of its 2018 revenue guide, Massaro added, and the company is looking to create some targeted digital ads to drive new doctor ordering for the test. The firm is also expecting payor decisions from France this summer, from Germany in the fall, and from the UK in September that could be affected by the study’s results.

Overall, Massaro is modeling 13 percent growth in revenues for Genomic Health in 2018, driven in part by the TAILORx results.

Cowen analyst Doug Schenkel in a note to investors on Monday added that the study “solidifies the utility of Oncotype in women with early-stage breast cancer, and it could drive increased ordering of Oncotype. Put simply, we see potential material upside to our volume and revenue per test forecasts in the US and abroad over the next several years.”

Schenkel also noted that Genomic Health believes it now has some power with insurers to improve reimbursement prices for its test, which could be important when its commercial contracts come up for renewal.

“We are currently forecasting that the Invasive Breast average revenue per test will increase by 3 percent in 2020 relative to 2018 levels. Based on company commentary and the disproportionate number of patients that are commercially covered (about 80 percent), we believe this forecast is very achievable if not beatable,” he wrote. “An increase in the reimbursement rate of 10 percent compared to today’s levels would lead to a $30 million increase in our 2020 estimated revenues, with all other assumptions unchanged.”

https://bit.ly/2HhgTzL

Bayer launches $7 billion cash call to fund Monsanto deal

Bayer launched a 6 billion euros ($7 billion/5.24 billion pounds) rights issue on Sunday, a cornerstone of the financing package for its planned $62.5 billion takeover of seeds maker Monsanto.

Bayer last week won U.S. approval for the Monsanto takeover, clearing a major hurdle for a deal that will create by far the largest seeds and pesticides maker.

The cash call is smaller than initially envisaged by Bayer because Monsanto reduced its debt while the antitrust review dragged on.

Also, Bayer raised 4.5 billion euros more from selling down its stake in plastics maker Covestro than initially expected.

The German drugmaker also grossed 7.6 billion euros in proceeds from selling assets to BASF, as the antitrust reviews were stricter than anticipated, but that did not cut the need to raise money via a share issue because future cash flows to service debts would also be lower.

When the merger was agreed in September 2016, Bayer said it would raise $19 billion worth of fresh equity capital for the takeover deal, parts of which was covered by issuing 4 billion euros in mandatory convertible notes in November 2016.

Bayer has said it would close the transaction very soon, which it needs to do because Monsanto could withdraw from the takeover agreement and seek a higher price after June 14.

Bayer is set to close the transaction on June 7, according to a media report on Sunday.

Bayer will create an agricultural supplies giant with sales of about 20 billion euros, based on 2017 figures, when taking into account the divestments.

At current foreign exchange rates, that compares to about 12.4 billion euros at DowDuPont Corteva Agriscience unit, 11 billion euros at ChemChina’s Syngenta and 7.9 billion at BASF, including businesses to be acquired.

https://bit.ly/2xF0Mg7

#ASCO18: Sanofi, Regeneron skin cancer med trial results ‘strong’

The New England Journal of Medicine published pivotal data from two trials evaluating cemiplimab in advanced cutaneous squamous cell carcinoma. The results were also presented at the 2018 American Society of Clinical Oncology Annual Meeting. Advanced CSCC, the deadliest nonmelanoma skin cancer, encompasses both patients with metastatic CSCC and those with locally advanced CSCC who are not candidates for surgery; there is currently no approved treatment for these patients. Cemiplimab is an investigational human monoclonal antibody targeting the immune checkpoint PD-1. “The strong results seen with cemiplimab are noteworthy given that advanced CSCC is a very serious condition that currently has no approved treatments once surgery is no longer an option,” said Michael R. Migden, M.D., co-lead author and Associate Professor in the Departments of Dermatology and Head and Neck Surgery at The University of Texas MD Anderson Cancer Center. “Advanced CSCC tumors were shown to be responsive to cemiplimab in both metastatic and locally advanced patients, with the results being clinically meaningful and consistent between the Phase 1 and Phase 2 trials.” Cemiplimab is being jointly developed by Sanofi (SNY) and Regeneron (REGN) under a global collaboration agreement.

https://bit.ly/2xJzDZe

#ASCO18: Cytomx safety seems improved in early data: Jefferies

CytomX early data point to some safety differentiation, says Jefferies. Jefferies analyst Biren Amin said he thinks some investors may have sought a better efficacy profile from CX-072. However, he notes that the Yervoy combo data provided at ASCO are in the dose-escalation phase and are in heavily pretreated patients, adding that safety seems improved with the CX-072 plus ipi combo. Amin has a Buy rating and $40 price target on CytomX shares, which are down $5.58, or 22%, to $19.96 in afternoon trading

https://bit.ly/2sArwbI

Stanford spinout Forty Seven arrives at #ASCO18 with promising data, $115M IPO

Here’s a neat trick for up-and-coming oncology biotechs to consider.

Execs for Forty Seven, the CD47 star founded by Stanford’s legendary Irv Weissman, filed for a $115 million IPO on Friday and then — instead of hunkering down for the quiet period — promptly flew out to Chicago to tout a promising set of proof-of-concept data for their lead drug at ASCO.

Forty Seven has preliminary data on 22 patients taking 5F9, with an impressive initial snapshot of early data for the small group. Fifteen of the patients suffer from treatment resistant diffuse large B-cell lymphoma (DLBCL) and the other 7 have follicular lymphoma. In DLBCL investigators tracked an objective response rate of 40% with a third achieving a complete response; in follicular lymphoma the ORR was 71% with 43% achieving a CR.

It’s still too early to set a median rate on the duration of response, but the researchers say that just 1 of the 22 saw their cancer progress after 6 months.

5F9 is an antibody that targets the popular CD47 receptor targets, which has inspired a slate of development efforts. Hitting that target is intended to scramble the “don’t-eat-me” signal that cancer cells rely on to avoid being chewed up by macrophages. And the Menlo Park, CA-based biotech has 6 studies underway in solid tumors, acute myeloid leukemia, non-Hodgkin’s lymphoma and colorectal carcinoma.

The biotech plans to push its studies ahead as a mono therapy as well as in combinations with PD-1/PD-L1 and CTLA-4 checkpoint inhibitors, starting with Genentech’s Tecentriq.

Forty Seven has an interesting past. The 78-year-old Weissman was able to wrangle substantial support for his early research work on CD47 from the California Institute for Regenerative Medicine, even launching early human studies — a rare feat in academic circles. Weissman and former CIRM chief Alan Trounson enjoyed a tight relationship, which extended to Trounson’s appointment to the board of another startup that Weissman had helped found — StemCells —shortly after his departure from the agency. And Forty Seven is still getting money from CIRM under its latest $19 million grant.

So far the company has raised $149 million and spent $84 million of that, according to the S-1.

Mark McCamish, a Novartis vet who enjoyed a $3.7 million pay package last year, is the CEO. He also has 3.6% of the stock. Lightspeed Ventures Partners and Sutter Hill Partners each control 16.8% of the stock, followed by Clarus at 15.8%. And Weissman has retained a hefty 9.5% of the equity, which could soon be worth a small fortune.

Forty Seven includes the following companies on its list of rivals in the field: Celgene Corporation, Trillium Therapeutics, Alexo Therapeutics, Arch Therapeutics, Surface Oncology, Novimmune, OSE Immunotherapeutics and Aurigene Discovery Technologies.

https://bit.ly/2JgNMyk

Vaxart reports Phase 2 defeat for a legacy antiviral from Aviragen

When Vaxart picked Aviragen Therapeutics for the reverse merger that got it on the Nasdaq, the South San Francisco biotech highlighted a Phase II treatment for condyloma caused by HPV as particularly interesting among the antiviral programs it was inheriting. Seven months later, Vaxart is finding out the drug, like many of Aviragen’s previous therapies, might be a failure after all.

Vaxart reports today that teslexivir (BTA074) has flunked the primary efficacy endpoint: complete clearance of baseline condyloma, or small bumps on genitals, by week 16. In a double blind trial evaluating the teslexivir 5% gel in 218 patients, only 30.6% of the drug arm — not a statistically significant difference from 23.3% in the placebo group — completely cleared baseline condyloma by week 16.

The news sent Vaxart’s stock $VXRT down 18.7% in pre-market trading, despite the company’s efforts to shine what positive light they had on the data.

Some of the patients who cleared all condyloma within the predetermined period have entered a three-month follow-up period to assess the recurrence efficacy endpoints. That’s part of the secondary efficacy endpoints, which include various assessments of clearance, time to clearance, and wart area reduction for both baseline warts and post-baseline emergent warts.

The company attempted to salvage the situation with a preliminary subgroup analysis of female patients and those with large condylomas, while noting neither of the results are significant. Female patients on teslexivir saw a 37.5% clearance rate versus 23.3% among those on placebo; for patients with large condylomas, the numbers were 30.0% (drug) and 15.4% (placebo).

“While this trial did not achieve the primary efficacy endpoint, we were pleased with the benign safety profile and positive efficacy trends in certain patient subpopulations,” said CEO Wouter Latour in a statement. “We are currently in the follow-up phase of the study and data collection should continue for a few more weeks. During this period, we will conduct further analysis of the results, which should inform us about the future steps with the teslexivir program. In the meantime, we will continue to focus on the advancement of our oral vaccine platform through the clinic.”

Under the leadership of new CMO David Taylor, Vaxart is marching onward with its signature oral vaccines intended to replace the injectables in use. It had a positive Phase II readout in January for its prophylactic influenza pill, and is hoping to do the same with a norovirus program.

https://bit.ly/2Lmk1wO