On April 18, 2020 MOMA Therapeutics reported that it has launched with $86 million in series A financing, led by Third Rock Ventures, to develop small-molecule drugs against a family of more than 400 proteins—MOMA calls them molecular machines—that use ATP hydrolysis to "generate force and motion (Press release, MOMA Therapeutics, APR 18, 2020, View Source,DNA%20helicases%20and%20chromatin%20remodeling [SID1234561265])." Examples include DNA helicases and chromatin remodeling proteins, which regulate gene expression. The company has recruited experts in protein biophysics and cryogenic electron microscopy to target molecular machines implicated in cancer and rare diseases.

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On April 18, 2020 Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax personalized immune therapies for solid tumor cancers, reported that its CEO, Linda Powers, will discuss the projected schedule for reaching data lock, unblinding and reporting of top line data from its 331-patient Phase 3 trial of DCVax-L for Glioblastoma brain cancer at the Company’s 2019 Annual Meeting (Press release, Northwest Biotherapeutics, APR 18, 2020, View Source [SID1234556422]). The Meeting is being held virtually due to the current public health crisis.

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The Company has been working since last year with the contract research organization (CRO) that managed the trial and numerous independent service companies to make the final in-person monitoring visits to all the clinical trial sites (hospitals) across the US and Europe, and to finish collecting and confirming the Phase 3 trial data and resolving queries.

Despite nearly two months (during March and April to date) in which hospital trial sites stopped allowing in-person data monitoring visits and became too overwhelmed to continue helping with data confirmation, the Company’s data collection and confirmation process has continued moving forward in part through workarounds.

The data collection process is including certain epigenetic and genetic information that is recognized as important in Glioblastoma, such as MGMT methylation status. As part of this process, the Company has also identified a method that can potentially enable an additional important genetic factor — IDH mutation status — to be analyzed using bio samples collected years ago during the trial, and to be analyzed in the same timeframe as the data lock. This IDH mutation factor was unknown when the Company’s trial began and through much of the trial period, but has become recognized as very important in recent years.

After factoring in the March and April shutdowns, and the additional genetic analysis, the Company believes it can reach data lock by approximately the end of May.

Upon reaching data lock, the data will be unblinded to the independent statisticians (i.e., the statisticians will be given access to the trial database containing all of the raw data points). The Company will not yet become unblinded at this time.

The independent statisticians will then use the raw data to calculate the relevant measures, such as median survival times and survival percentages at various time points. The statisticians will also calculate various statistical measures and prepare graphs and tables. This work is anticipated to take several weeks. The Company will become unblinded when it receives these results from the statisticians.

The Company will then discuss the information from the statisticians with its expert advisors, including its Scientific Advisory Board and the Steering Committee of the Phase 3 trial. Any questions or comments raised by the experts will be addressed and the results will be prepared for public announcement.

Based on these expectations, and taking account of the two months lost in March and April, the current estimate of public disclosure of top line data would range from the end of June to early July.

On Apr. 17, 2020 Incyte (Nasdaq:INCY) reported the initiation of RUXCOVID, a global, randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy and safety of ruxolitinib (Jakafi) plus standard-of-care (SoC) in patients aged ≥12 years with COVID-19 associated cytokine storm. The collaborative study is sponsored by Incyte in the United States and Novartis outside of the United States.

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The composite primary endpoint is the proportion of patients who die, develop respiratory failure (require mechanical ventilation) or require intensive care unit (ICU) care by Day 29. Secondary endpoints comprise various efficacy assessments including evaluation of clinical status using a 9-point ordinal scale; in-hospital outcomes (mortality rate; proportion of patients requiring mechanical ventilation; duration of hospitalization, ICU stay, supplemental oxygen, invasive mechanical ventilation); change in the National Early Warning Score (NEWS2); change in SpO2/FiO2 ratio; proportion of patients with no oxygen therapy (oxygen saturation of ≥94% on room air); and safety. RUXCOVID will enroll approximately 400 patients globally.

Additionally, given the urgent nature of the COVID-19 pandemic, Incyte is also initiating a separate emergency Expanded Access Program (EAP) in the United States. The protocol will allow eligible patients with severe COVID-19 associated cytokine storm to receive ruxolitinib while it is being investigated for this indication.

"There is an unprecedented unmet medical need for treatments that prevent or reduce severe COVID-19 related complications to improve outcomes for patients and alleviate the overwhelming pressure on the global healthcare system," said Steven Stein, M.D., Chief Medical Officer, Incyte. "We thank the FDA for the expedited review of the RUXCOVID study and hope to enroll this important clinical trial as quickly as possible to determine the potential utility of ruxolitinib for treatment of patients with severe COVID-19 associated cytokine storm."

RUXCOVID is the first Phase 3, randomized, placebo-controlled study designed to evaluate the efficacy and safety of ruxolitinib in patients with COVID-19 associated cytokine storm.

At present, there is ample commercial and clinical supply of ruxolitinib in the United States to meet the needs of U.S. patients receiving ruxolitinib in its approved indications and those participating in clinical trials. Incyte is increasing manufacturing efforts to respond to anticipated supply needs related to COVID-19 studies and working closely with distribution partners to monitor the supply of ruxolitinib.

About COVID-19 Associated Cytokine Storm
Cytokine storm is a severe immune overreaction that can be triggered by a viral infection and can lead to serious complications, including pneumonia and acute respiratory distress syndrome (ARDS). Patients with COVID-19 associated cytokine storm who experience these complications often require intensive care, including intubation and the use of mechanical ventilation, and are at an increased risk of mortality.

Emerging evidence suggests that regulating overactive signaling through the JAK-STAT pathway during a cytokine storm associated with COVID-19 could be a potential treatment approach, and it is hypothesized that ruxolitinib, a JAK1/JAK2 inhibitor, may be able to play a role in treating these patients.

Currently, there is limited clinical evidence on the safety and efficacy of ruxolitinib for the treatment of COVID-19 associated cytokine storm, and ruxolitinib is not FDA-approved for this use.

About RUXCOVID
RUXCOVID is a global, randomized, double-blind, placebo-controlled, 29-day, multi-center Phase 3 study evaluating the efficacy and safety of ruxolitinib plus standard of care (SoC) therapy in patients aged ≥12 years with COVID-19 associated cytokine storm compared to placebo plus SoC therapy.

The composite primary endpoint is the proportion of patients who die, develop respiratory failure (require mechanical ventilation), or require intensive care unit (ICU) care by Day 29. Secondary endpoints are comprised of various efficacy assessments including evaluation of clinical status using a 9-point ordinal scale; in-hospital outcomes (mortality rate; proportion of patients requiring mechanical ventilation; duration of hospitalization, ICU stay, supplemental oxygen, invasive mechanical ventilation); change in the National Early Warning Score (NEWS2); change in SpO2/FiO2 ratio; proportion of patients with no oxygen therapy (oxygen saturation of ≥94% on room air); and safety.

Eligible patients will be randomized 2:1 to receive oral ruxolitinib 5mg twice daily (BID) or oral-matching placebo for a total of 14 days. Study treatment will be given in combination with SoC therapy according to the investigator’s clinical judgement. After 14 days of therapy, should clinical signs or symptoms not improve or worsen, and the potential benefit outweighs the potential risks, patients may receive an additional 14 days of study therapy. In total, patients will be followed on study for 29 days post-randomization.

The RUXCOVID study is sponsored by Incyte in the United States, and Novartis outside of the United States.

About the Ruxolitinib Expanded Access Program (EAP) in COVID-19
The ruxolitinib Expanded Access Program (EAP) in COVID-19 for patients with severe COVID-19 associated cytokine storm allows eligible patients to receive ruxolitinib while it is being investigated in COVID-19 patients. Patients must be unable to participate in other clinical trials of ruxolitinib in COVID-19 to qualify for this EAP.

On April 17, 2020 Incyte (Nasdaq:INCY) reported that the U.S. Food and Drug Administration (FDA) has approved Pemazyre (pemigatinib), a kinase inhibitor indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test (Press release, Incyte, APR 17, 2020, View Source [SID1234556414]). Pemazyre is the first and only FDA-approved treatment for this indication, which was approved under accelerated approval based on overall response rate and duration of response (DOR). Continued approval may be contingent on verification and description of clinical benefit in a confirmatory trial(s).

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"Although cholangiocarcinoma is considered a rare disease, it has been on the rise over the past three decades"

"Our research into FGFR2 fusions or rearrangements in cholangiocarcinoma and the development of Pemazyre as the first targeted treatment option demonstrates our commitment to translating scientific discovery into solutions that can positively impact patients’ lives," said Hervé Hoppenot, Chief Executive Officer, Incyte. "We’re proud to bring Pemazyre to patients and will make this new treatment available immediately."

The FDA approval was based on data from the FIGHT-202 study, a multi-center, open-label, single-arm study that evaluated Pemazyre as a treatment for adults with cholangiocarcinoma. In patients harboring FGFR2 fusions or rearrangements (Cohort A), Pemazyre monotherapy resulted in an overall response rate of 36% (primary endpoint), and median DOR of 9.1 months (secondary endpoint). Warnings and precautions for Pemazyre include eye problems such as dry or inflamed eyes, inflamed cornea, increased tears and a disorder of the retina; high levels of phosphate in the blood; and, for women who are pregnant, a risk of harm to the unborn baby or loss of pregnancy.

The FDA granted Pemazyre Breakthrough Therapy designation for the treatment of patients with previously treated advanced/metastatic or unresectable FGFR2 translocated cholangiocarcinoma. Additionally, the FDA granted Pemazyre Orphan Drug designation for the treatment of cholangiocarcinoma, and the New Drug Application (NDA) for Pemazyre was reviewed under the FDA’s Priority Review program.

"Although cholangiocarcinoma is considered a rare disease, it has been on the rise over the past three decades,"1,2 said Ghassan Abou-Alfa, M.D., Memorial Sloan Kettering Cancer Center. "It is encouraging to have a new targeted treatment option for patients who historically have had limited options after first-line chemotherapy or surgery, in which relapse rates remain high."

Cholangiocarcinoma is a rare cancer that forms in the bile duct. It is classified based on its anatomical origin: intrahepatic cholangiocarcinoma (iCCA) occurs in the bile duct inside the liver and extrahepatic cholangiocarcinoma occurs in the bile duct outside the liver. Patients with cholangiocarcinoma are often diagnosed at a late or advanced stage when the prognosis is poor.3,4 The incidence of cholangiocarcinoma varies regionally and ranges between 0.3-3.4 per 100,000 in North America and Europe.3 FGFR2 fusions or rearrangements occur almost exclusively in iCCA, where they are observed in 10-16% of patients.5-7 FGFRs play an important role in tumor cell proliferation and survival, migration and angiogenesis (the formation of new blood vessels). Activating fusions, rearrangements, translocations and gene amplifications in FGFRs are closely correlated with the development of various cancers.

"Today’s approval of Pemazyre provides an exciting new treatment option for patients and will bring hope to those who typically face a difficult diagnosis journey and poor prognosis," said Stacie Lindsey, President, Cholangiocarcinoma Foundation.

Incyte is committed to supporting patients and removing barriers to access medicines. Eligible patients in the U.S. who are prescribed Pemazyre have access to IncyteCARES (Connecting to Access, Reimbursement, Education and Support), a comprehensive program offering patient support, including financial assistance and ongoing education and resources to eligible patients. More information is available at Pemazyre.com.

The FDA is also expected to approve FoundationOneCDx as the companion diagnostic for Pemazyre. FoundationOne CDx is Foundation Medicine’s comprehensive genomic profiling assay and broad companion diagnostic platform approved for all solid tumors. If approved, this companion diagnostic would help identify patients with FGFR2 fusions or rearrangements who may be eligible for Pemazyre.

Conference Call Information

Incyte will host an investor conference call and webcast on Monday, April 20, 2020, at 8:00 a.m. ET. The webcast will be available via investor.incyte.com.

To access the conference call, please dial 877-407-3042 for domestic callers or +1-201-389-0864 for international callers. When prompted, provide the conference identification number 13700772.

If you are unable to participate, a replay of the conference call will be available for 30 days. The replay dial-in number for the United States is 877-660-6853 and the dial-in number for international callers is +1-201-612-7415. To access the replay, you will need the conference identification number 13700772.

About FIGHT-202

The FIGHT-202 Phase 2 multi-center, open-label, single-arm study (NCT02924376) evaluated the safety and efficacy of Pemazyre – a selective fibroblast growth factor receptor (FGFR) inhibitor – in adult (age ≥18 years) patients with previously treated, locally advanced or metastatic cholangiocarcinoma with documented FGFR2 fusion or rearrangement.

Patients were enrolled into one of three cohorts – Cohort A (FGFR2 fusions or rearrangements), Cohort B (other FGF/FGFR genetic alterations) or Cohort C (no FGF/FGFR genetic alterations). All patients received 13.5 mg Pemazyre orally once daily (QD) on a 21-day cycle (two weeks on/one week off) until radiological disease progression or unacceptable toxicity.

The primary endpoint of FIGHT-202 was overall response rate (ORR) in Cohort A, assessed by independent review per RECIST v1.1. Secondary endpoints include ORR in Cohorts B, A plus B, and C; and duration of response (DOR).

For more information about FIGHT-202, visit View Source

About FIGHT

The FIGHT (FIbroblast Growth factor receptor in oncology and Hematology Trials) clinical trial program includes ongoing Phase 2 and 3 studies investigating the safety and efficacy of Pemazyre therapy across several FGFR-driven malignancies. Phase 2 monotherapy studies include FIGHT-202, as well as FIGHT-201 investigating Pemazyre in patients with metastatic or surgically unresectable bladder cancer, including with activating FGFR3 mutations or fusions/rearrangements; FIGHT-203 in patients with myeloproliferative neoplasms with activating FGFR1 fusions/rearrangements; FIGHT-207 in patients with previously treated, locally-advanced/metastatic or surgically unresectable solid tumor malignancies harboring activating FGFR mutations or fusions/rearrangements, irrespective of tumor type. FIGHT-205 is a Phase 2 study investigating Pemazyre plus pembrolizumab combination therapy and Pemazyre monotherapy in patients with previously untreated, metastatic or unresectable bladder cancer harboring FGFR3 mutations or fusions/rearrangements who are not eligible to receive cisplatin. FIGHT-302 is a Phase 3 study investigating Pemazyre as a first-line treatment for patients with cholangiocarcinoma with FGFR2 fusions or rearrangements.

About Pemazyre (pemigatinib)

Pemazyre is a kinase inhibitor indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.

Pemazyre is a potent, selective, oral inhibitor of FGFR isoforms 1, 2 and 3 which, in preclinical studies, has demonstrated selective pharmacologic activity against cancer cells with FGFR alterations.

Pemazyre is marketed by Incyte in the United States. Incyte has granted Innovent Biologics, Inc. rights to develop and commercialize pemigatinib in hematology and oncology in Mainland China, Hong Kong, Macau and Taiwan. Incyte has retained all other rights to develop and commercialize pemigatinib outside of the United States.

Additionally, Incyte’s marketing authorization application (MAA) seeking the approval of pemigatinib for patients with cholangiocarcinoma in the EU has been validated by the European Medicines Agency (EMA) and is currently under review for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that is relapsed or refractory after at least one line of systemic therapy.

Pemazyre is a registered trademark of Incyte Corporation.

Important Safety Information

Before you take PEMAZYRE, tell your healthcare provider about all of your medical conditions, including if you:

have vision or eye problems
have problems swallowing tablets
are pregnant or plan to become pregnant. PEMAZYRE can harm your unborn baby or cause loss of your pregnancy (miscarriage). You should not become pregnant during treatment with PEMAZYRE.
Females who can become pregnant:

Your healthcare provider should do a pregnancy test before you start treatment with PEMAZYRE.
You should use an effective method of birth control during treatment and for 1 week after your final dose of PEMAZYRE. Talk to your healthcare provider about birth control methods that may be right for you.
Tell your healthcare provider right away if you become pregnant or think that you may be pregnant.
Males with female partners who can become pregnant:

You should use effective birth control when sexually active during treatment with PEMAZYRE and for 1 week after your final dose of PEMAZYRE.
are breastfeeding or plan to breastfeed. Do not breastfeed during treatment and for 1 week after your final dose of PEMAZYRE.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What are the possible side effects of PEMAZYRE?

PEMAZYRE may cause serious side effects, including:

Eye problems. Certain eye problems are common with PEMAZYRE but can also be serious. Eye problems include dry eye or inflamed eyes, inflamed cornea (front part of the eye), increased tears, and a disorder of the retina (an internal part of the eye). You will need to see an eye specialist for a complete eye exam before you begin treatment with PEMAZYRE, every 2 months for the first 6 months, and then every 3 months during treatment with PEMAZYRE.
You should use artificial tears or substitutes, hydrating or lubricating eye gels as needed, to help prevent or treat dry eyes.
Tell your healthcare provider right away if you develop any changes in your vision during treatment with PEMAZYRE, including: blurred vision, flashes of light, or see black spots. You may need to see an eye specialist right away.
High phosphate levels in your blood (hyperphosphatemia). Hyperphosphatemia is common with PEMAZYRE but can also be serious. Your healthcare provider will check your blood phosphate levels during treatment with PEMAZYRE.
Your healthcare provider may prescribe changes in your diet or phosphate lowering therapy, or change, interrupt, or stop PEMAZYRE if needed.
Tell your healthcare provider right away if you develop any muscle cramps, or numbness or tingling around your mouth.
The most common side effects of PEMAZYRE include:

hair loss
diarrhea
nails separate from the bed or poor formation of the nail
feeling tired
change in sense of taste
nausea
constipation
mouth sores
dry eyes
dry mouth
decrease in appetite
vomiting
joint pain
stomach-area (abdominal) pain
low phosphate in blood
back pain
dry skin
These are not all the possible side effects of PEMAZYRE. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects.

You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Incyte Medical Information at 1-855-463-3463.

General information about the safe and effective use of PEMAZYRE.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use PEMAZYRE for a condition for which it is not prescribed. Do not give PEMAZYRE to other people, even if they have the same symptoms you have. It may harm them. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information that is written for healthcare professionals. Keep PEMAZYRE and all medicines out of the reach of children.

On April 17, 2020 Varian (NYSE: VAR) reported its second quarter fiscal year 2020 earnings release date (Press release, Varian Medical Systems, APR 17, 2020, View Source [SID1234556412]).

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The Company will report results for the second quarter of fiscal year 2020 after market close on Monday, May 4, 2020. The news release will be followed by a teleconference available to all interested at 1:30 p.m. Pacific Time. To access the teleconference call and replay:

Teleconference: Access from within the U.S. by dialing 1-877-869-3847, and from outside the U.S. by dialing 1-201-689-8261.

Replay: Access from within the U.S. by dialing 1-877-660-6853 and from outside the U.S. by dialing 1-201-612-7415 and enter conference ID 13700412. The teleconference replay will be available until 5:00 p.m. Pacific Time, Friday, May 8, 2020.

Webcast: To access the live webcast and replay, visit the company website at: www.varian.com/investors and click on the link for Second Quarter Earnings Results.

For automatic e-mail alerts regarding Varian news and events, investors can subscribe on the company website: View Source