On March 7, 2019 Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of medicines that control the expression of genes, reported financial results for the fourth quarter and full year ended December 31, 2018 and provided an update on recent accomplishments and upcoming events (Press release, Syros Pharmaceuticals, MAR 7, 2019, View Source [SID1234534082]).

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"Our accomplishments in 2018 position us for multiple potential clinical milestones in 2019 and 2020 that bring us closer to our vision of building a fully integrated company with medicines that provide a profound benefit for patients," said Nancy Simonian, M.D., Chief Executive Officer of Syros. "Building on promising clinical data for both our lead programs, we plan to expand our ongoing Phase 2 trial of SY-1425 in combination with azacitidine with the addition of a cohort in RARA and IRF8 biomarker-positive relapsed or refractory AML patients. We have also added a cohort of recurrent ovarian clear cell cancer patients to our ongoing Phase 1 trial of SY-1365. The unmet need in both these patient populations is significant, and we believe these cohorts could lead to rapid clinical proof-of-concept. These new cohorts, when combined with our ongoing evaluation of SY-1365 as a single agent in patients with high-grade serous ovarian cancer, give us three potential fast-to-market opportunities for our lead programs. We are focused on executing on our clinical trials with the aim of delivering much-needed therapies to patients as quickly as possible."

Upcoming Milestones:

SY-1425

Syros announced today that it plans to expand its ongoing Phase 2 trial to assess the safety and efficacy of SY-1425 in combination with azacitidine in RARA or IRF8 biomarker-positive patients with relapsed or refractory acute myeloid leukemia (AML). The Company expects this expansion to be open for enrollment in the third quarter.
Syros plans to complete enrollment in mid-2019 in the ongoing Phase 2 trial cohort evaluating the safety and efficacy of SY-1425 in combination with azacitidine in RARA or IRF8 biomarker-positive patients with newly diagnosed AML who are not suitable candidates for standard chemotherapy.
Syros plans to report updated data in the second half of 2019 from the ongoing Phase 2 trial of SY-1425 in combination with azaciditine in newly diagnosed unfit AML patients.
SY-1365

Syros announced today that it has added an expansion cohort to its ongoing Phase 1 trial of SY-1365 to evaluate its safety and efficacy as a single agent in patients with recurrent ovarian clear cell cancer. The Company expects the cohort to be open for enrollment in the second quarter of 2019. This cohort will replace the cohort evaluating SY-1365 in patients with primary platinum refractory ovarian cancer.
Syros plans to report initial clinical data in the fourth quarter of 2019 from the expansion portion of its ongoing Phase 1 trial. These data are expected to include initial efficacy and safety assessments from the cohort evaluating SY-1365 as a single agent in high-grade serous ovarian cancer patients who have had three or more prior lines of therapy; initial safety and pharmacokinetic data from the cohort evaluating SY-1365 in combination with carboplatin in high-grade serous ovarian cancer patients who have had one or more prior lines of therapy; and initial safety, efficacy and mechanistic data from the cohort evaluating SY-1365 as a single agent in patients with advanced solid tumors accessible for biopsy.
SY-5609

Syros plans to complete investigational new drug-enabling studies of SY-5609 in 2019 to support the initiation of a Phase 1 oncology trial in early 2020.
Recent Pipeline Highlights:

In December 2018, Syros’ collaborators presented new preclinical data on SY-1365 at the San Antonio Breast Cancer Symposium (SABCS). The data showed that SY-1365 inhibits tumor cell growth in hormone receptor-positive (HR-positive) breast cancer cell lines that are resistant to treatment with CDK4/6 inhibitors and that SY-1365 has synergistic activity in combination with fulvestrant in these treatment-resistant cells.
In December 2018, Syros presented initial clinical data from cohorts in its ongoing Phase 2 trial evaluating SY-1425 in combination with azacitidine at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. SY-1425 in combination with azacitidine showed high response rates and rapid onset of action in biomarker-positive patients with newly diagnosed unfit AML as of an October 29, 2018 data cut-off. The data showed:
The aggregate complete response (CR) and complete response with incomplete blood count recovery (CRi) rate was 50% in biomarker-positive patients (n=8), and the overall response rate (ORR) was 63%.
Most initial responses in biomarker-positive patients were seen at the end of the first treatment cycle, and duration of responses ranged from 29 to 337 days, with four of five responding patients remaining on treatment.
The ORR was 17% in biomarker-negative patients (n=6). While the data from this cohort were less mature due to the timing of patient enrollment, Syros believes that the difference in the observed ORR supports the potential predictive value of the RARA and IRF8 biomarkers for identifying patients most likely to respond to SY-1425.
The combination was generally well-tolerated, with no evidence of increased toxicities beyond what has been seen with either agent alone, including myelosuppression, which can occur when combining drugs to treat AML.
In December 2018, Syros also presented initial clinical data from a Phase 2 study cohort evaluating SY-1425 in combination with daratumumab in biomarker-positive patients with relapsed or refractory AML and higher-risk myelodysplastic syndrome at ASH (Free ASH Whitepaper). While the data showed that SY-1425 induced CD38 expression in eight of nine evaluable patients, CD38 expression increased to levels exceeding those of a multiple myeloma cell line control in only two of these patients. Of those two, one had a morphological leukemia-free state (MLFS) response. Based on these data, Syros made a portfolio prioritization decision not to pursue further development of SY-1425 in combination with daratumumab.
In November 2018, Syros presented clinical data from the dose escalation portion of its Phase 1 trial of SY-1365 in patients with advanced solid tumors at the 30th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium (EORTC-NCI-AACR) (Free EORTC-NCI-AACR Whitepaper). The data showed proof-of-mechanism and early signs of clinical activity at tolerable doses:
Clinical activity was observed in seven of 19 response-evaluable patients, including one patient with recurrent ovarian clear cell cancer who had a confirmed partial response (PR) and six additional patients who had stable disease (SD).
Dose-dependent effects on CDK7 occupancy and downstream gene expression changes in blood cells were observed.
At doses of 32 mg/m2 and higher, CDK7 occupancy was greater than 50% when measured three days following dose administration, exceeding target occupancy levels in preclinical models that correlated with anti-tumor activity.
Adverse events were predominately low-grade, reversible and manageable.
Also at EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper), Syros presented preclinical data on SY-1365 showing synergistic anti-tumor activity in combination with carboplatin in ovarian cancer cell lines and decreased expression of DNA damage response genes, providing a mechanistic rationale for the ongoing investigation of SY-1365 in combination with carboplatin in ovarian cancer patients.
Additionally, Syros presented the first preclinical data from its oral CDK7 program, detailing the selectivity, potency and anti-tumor activity of several compounds and supporting the selection of SY-5609, an oral CDK7 inhibitor, as a development candidate.
Recent Corporate Highlights:

In December 2018, Syros announced that it had been added to the NASDAQ Biotechnology Index (NASDAQ: NBI), effective Monday, December 24, 2018.
Fourth Quarter 2018 Financial Results

Cash, cash equivalents and marketable securities as of December 31, 2018 were $99.7 million, compared with $72.0 million on December 31, 2017.

For the fourth quarter of 2018, Syros reported a net loss of $18.0 million, or $0.54 per share, compared to a net loss of $15.3 million, or $0.58 per share, for the same period in 2017.

Revenues were $0.9 million for the fourth quarter of 2018, which relate entirely to Syros’ target discovery collaboration with Incyte Corporation. Syros did not record revenues in the fourth quarter of 2017.
Research and development (R&D) expenses were $15.1 million for the fourth quarter of 2018, as compared to $11.8 million for the same period in 2017. This increase was primarily attributable to an increase in SY-1365 contract manufacturing costs and professional fees in support of Syros’ clinical trials, as well as an increase in employee-related expenses.
General and administrative (G&A) expenses were $4.4 million for the fourth quarter of 2018, as compared to $3.7 million for the same period in 2017. This increase was primarily attributable to an increase in employee-related expenses.
Full Year 2018 Financial Results

For the full year ended December 31, 2018, Syros reported a net loss of $62.3 million, or $1.91 per share, compared to a net loss of $54.0 million, or $2.13 per share, for the same period in 2017.

Revenues for the year ended December 31, 2018 were $2.1 million, as compared to $1.1 million for the same period in 2017. Revenues earned in 2018 related entirely to the Incyte collaboration. Revenues earned in 2017 were earned from a research agreement with a multinational pharmaceutical company.
R&D expenses for the year ended December 31, 2018 were $50.2 million, as compared to $41.9 million for the same period in 2017. This increase was primarily attributable to an increase in contract manufacturing costs and professional fees in support of Syros’ clinical trials, as well as an increase in employee-related expenses.
G&A expenses for the year ended December 31, 2018 were $16.2 million, as compared to $13.9 million for the same period in 2017. This increase was primarily attributable to an increase in employee-related expenses.
Financial Guidance

Based on its current plans, Syros believes that its existing cash, cash equivalents and marketable securities will be sufficient to fund its planned operating expenses and capital expenditure requirements into the second quarter of 2020.

Conference Call and Webcast:

Syros will host a conference call today at 8:30 a.m. ET to discuss these fourth quarter and full year 2018 financial results and provide a corporate update.

The live call may be accessed by dialing (866) 595-4538 for domestic callers or (636) 812-6496 for international callers and referencing conference ID number: 7258556. A live webcast of the conference call will be available online on the Investors & Media section of the Syros website at www.syros.com. An archived replay of the webcast will be available for approximately 90 days.

On March 7, 2019 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) granted a fifth Breakthrough Therapy Designation (BTD) to venetoclax, for use in combination with obinutuzumab as a fixed duration investigational combination, for untreated adult patients with chronic lymphocytic leukemia (CLL) (Press release, AbbVie, MAR 7, 2019, View Source [SID1234534103]). According to the FDA, this designation is intended to expedite the review of therapies for serious or life-threatening conditions. The designation coincides with the completion of the supplemental New Drug Application (sNDA) submission to the FDA for approval in previously-untreated CLL patients.

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The FDA will review the venetoclax and obinutuzumab combination under its Real-Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process to ensure safe and effective cancer medicines are available to patients as early as possible.

"We studied the venetoclax and obinutuzumab combination with a fixed treatment duration and found these medicines, used together, may enable some CLL patients to live longer without their disease getting worse, leading to longer progression-free survival, while remaining off therapy," said Mohamed Zaki, M.D., Ph.D., vice president, global head of hematology development, AbbVie. "Under the RTOR program, we are determined to work with the FDA and bring this first- and only-in-class medicine to previously-untreated CLL patients earlier than expected."

The sNDA for the venetoclax and obinutuzumab combination is based on data from the Phase 3 CLL14 trial, which studied patients receiving the combination treatment for 12 months as their first treatment for CLL. CLL14 is the first randomized trial in CLL to examine a chemotherapy-free, fixed duration treatment regimen.

The FDA’s standard review time for drug applications is six to 10 months.1 The RTOR program focuses on the early submission of data most relevant to assessing the product’s safety and effectiveness. RTOR allows the FDA to review much of the data before it is formally submitted to the FDA.

VENCLEXTA (venetoclax) is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

About Chronic Lymphocytic Leukemia
CLL is typically a slow-progressing cancer of the bone marrow and blood in which types of white blood cells called B lymphocytes become cancerous and multiply abnormally.2 In the U.S., CLL accounts for more than 20,000 newly diagnosed cases of leukemia each year.2

About the Phase 3 CLL14 Trial
The prospective, multicenter, open-label, randomized Phase 3 CLL14 trial, which was conducted in close collaboration with the German CLL Study Group (DCLLSG), evaluated the efficacy and safety of a combined regimen of venetoclax and obinutuzumab (n=216) versus obinutuzumab and chlorambucil (n=216) in previously-untreated patients with CLL and coexisting medical conditions. The therapies were administered for a fixed duration of 12 months for venetoclax in combination with six cycles of obinutuzumab. The trial enrolled 445 patients, all of whom were previously-untreated according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria. The primary endpoint was progression-free survival (PFS) based on investigator assessment, using iwCLL criteria.3

Key secondary endpoints were PFS as assessed by an independent review committee, minimal residual disease (MRD)-negativity in peripheral blood and bone marrow, overall and complete response rates, MRD-negativity in complete response in peripheral blood and bone marrow, and overall survival.

About VENCLEXTA (venetoclax tablets) (US)
VENCLEXTA is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis. VENCLEXTA targets the BCL-2 protein and works to help restore the process of apoptosis.4

VENCLEXTA is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research and to studying venetoclax in clinical trials across several blood and other cancers.

The efficacy and safety of venetoclax in patients with previously-untreated CLL has not been evaluated by the U.S. Food and Drug Administration, the European Medicines Agency or any health authority.

In April 2016, the U.S. FDA first granted accelerated approval of VENCLEXTA for the treatment of patients with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy.5 The FDA approved this indication under accelerated approval based on overall response rate.5 Based on the results of the MURANO study, VENCLEXTA was approved in June 2018 for the treatment of patients with CLL or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy.4 In November 2018, VENCLEXTA was approved in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly-diagnosed acute myeloid leukemia (AML) who are 75 years of age or older, or have other medical conditions that prevent the use of standard chemotherapy.6

Venetoclax is approved in more than 50 countries, including the U.S. AbbVie, in collaboration with Roche, is currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.

Uses and Important Safety Information (US)

Uses

VENCLEXTA is a prescription medicine used:

to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior treatment.
in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly-diagnosed acute myeloid leukemia (AML) who:
are 75 years of age or older, or
have other medical conditions that prevent the use of standard chemotherapy.
It is not known if VENCLEXTA is safe and effective in children.

Important Safety Information

What is the most important information I should know about VENCLEXTA?

VENCLEXTA can cause serious side effects, including:

Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. Your healthcare provider will do tests to check your risk of getting TLS before you start taking VENCLEXTA. You will receive other medicines before starting and during treatment with VENCLEXTA to help reduce your risk of TLS. You may also need to receive intravenous (IV) fluids into your vein. Your healthcare provider will do blood tests to check for TLS when you first start treatment and during treatment with VENCLEXTA.

It is important to keep your appointments for blood tests. Tell your healthcare provider right away if you have any symptoms of TLS during treatment with VENCLEXTA, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain.

Drink plenty of water when taking VENCLEXTA to help reduce your risk of getting TLS.
Drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before your first dose, on the day of your first dose of VENCLEXTA, and each time your dose is increased.
Your healthcare provider may delay, decrease your dose, or stop treatment with VENCLEXTA if you have side effects.

Who should not take VENCLEXTA?

Certain medicines must not be taken when you first start taking VENCLEXTA and while your dose is being slowly increased because of the risk of increased TLS.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. VENCLEXTA and other medicines may affect each other, causing serious side effects.
Do not start new medicines during treatment with VENCLEXTA without first talking with your healthcare provider.
Before taking VENCLEXTA, tell your healthcare provider about all of your medical conditions, including if you:

have kidney problems.
have problems with your body salts or electrolytes, such as potassium, phosphorus, or calcium.
have a history of high uric acid levels in your blood or gout.
are scheduled to receive a vaccine. You should not receive a "live vaccine" before, during, or after treatment with VENCLEXTA, until your healthcare provider tells you it is okay. If you are not sure about the type of immunization or vaccine, ask your healthcare provider. These vaccines may not be safe or may not work as well during treatment with VENCLEXTA.
are pregnant or plan to become pregnant. VENCLEXTA may harm your unborn baby. If you are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with VENCLEXTA, and you should use effective birth control during treatment and for 30 days after the last dose of VENCLEXTA. If you become pregnant or think you are pregnant, tell your healthcare provider right away.
are breastfeeding or plan to breastfeed. It is not known if VENCLEXTA passes into your breast milk. Do not breastfeed during treatment with VENCLEXTA.
What should I avoid while taking VENCLEXTA?
You should not drink grapefruit juice or eat grapefruit, Seville oranges (often used in marmalades), or starfruit while you are taking VENCLEXTA. These products may increase the amount of VENCLEXTA in your blood.

What are the possible side effects of VENCLEXTA?

VENCLEXTA can cause serious side effects, including:

Low white blood cell counts (neutropenia). Low white blood cell counts are common with VENCLEXTA, but can also be severe. Your healthcare provider will do blood tests to check your blood counts during treatment with VENCLEXTA. Tell your healthcare provider right away if you have a fever or any signs of an infection during treatment with VENCLEXTA.
The most common side effects of VENCLEXTA when used in combination with rituximab in people with CLL include low white blood cell counts, diarrhea, upper respiratory tract infection, cough, tiredness, and nausea.

The most common side effects of VENCLEXTA when used alone in people with CLL/SLL include low white blood cell counts; diarrhea; nausea; upper respiratory tract infection; low red blood cell counts; tiredness; low platelet counts; muscle and joint pain; swelling of your arms, legs, hands, and feet; and cough.

The most common side effects of VENCLEXTA in combination with azacitidine, or decitabine, or low-dose cytarabine in people with AML include low white blood cell counts; nausea; diarrhea; low platelet counts; constipation; fever with low white blood cell counts; low red blood cell counts, infection in blood; rash; dizziness; low blood pressure; fever; swelling of your arms, legs, hands, and feet; vomiting; tiredness; shortness of breath; bleeding; infection in lung; stomach (abdominal) pain; pain in muscles or back; cough; and sore throat.

VENCLEXTA may cause fertility problems in males. This may affect your ability to father a child. Talk to your healthcare provider if you have concerns about fertility.

These are not all the possible side effects of VENCLEXTA. For more information, ask your healthcare provider or pharmacist.

You are encouraged to report negative side effects of prescription drugs to the FDA.

Visit View Source or call 1-800-FDA-1088.

If you cannot afford your medication, contact: www.pparx.org for assistance.

The full U.S. prescribing information, including Medication Guide, for VENCLEXTA can be found here. Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie in Oncology
At AbbVie, we strive to discover and develop medicines that deliver transformational improvements in cancer treatment by uniquely combining our deep knowledge in core areas of biology with cutting-edge technologies, and by working together with our partners – scientists, clinical experts, industry peers, advocates, and patients. We remain focused on delivering these transformative advances in treatment across some of the most debilitating and widespread cancers. We are also committed to exploring solutions to help patients obtain access to our cancer medicines. With the acquisitions of Pharmacyclics in 2015 and Stemcentrx in 2016, our research and development efforts, and through collaborations, AbbVie’s oncology portfolio now consists of marketed medicines and a pipeline containing multiple new molecules being evaluated worldwide in more than 200 clinical trials and more than 20 different tumor types. For more information, please visit View Source

On March 7, 2019 MorphoSys AG (FSE: MOR; Prime Standard Segment; MDAX & TecDAX; Nasdaq: MOR) reported updates on L-MIND and B-MIND, its two ongoing clinical trials of the investigational Fc-enhanced anti-CD19 antibody MOR208 in patients with relapsed or refractory diffuse large B cell lymphoma (r/r DLBCL), who are not eligible for high-dose chemotherapy and autologous stem cell transplantation (Press release, MorphoSys, MAR 7, 2019, View Source [SID1234534128]).

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The L-MIND trial, the Company’s single-arm, open-label study investigating MOR208 in combination with lenalidomide, has completed enrollment and data are currently being analyzed. Topline results are expected to be released at a medical conference in mid-2019. The Company intends to use L-MIND as the basis for a regulatory filing to the FDA, which it expects to complete by the end of this year. In parallel, the Company has initiated discussions with National European Regulatory Authorities to explore the possibility of using the L-MIND study as the basis for the submission of a potential marketing authorization application (MAA) in Europe. If the European Medicines Agency (EMA) were to agree to accept a potential MAA based on L-MIND, submission of such an MAA could occur earlier than originally anticipated based on the B-MIND trial. MorphoSys is seeking scientific advice from EMA in the forthcoming months.

The B-MIND study, which compares MOR208 in combination with bendamustine versus rituximab plus bendamustine, continues as originally designed. Additionally, during the first quarter of 2019 and in agreement with the FDA, MorphoSys implemented an amendment of the B-MIND study. The scientific rationale for the amendment is based on published literature as well as MorphoSys’s own pre-clinical data, which indicate that MOR208 might be particularly active in patients who can be characterized by the presence of a certain biomarker. The amended B-MIND trial may serve, in addition to being potentially pivotal on its own, as a confirmatory study if conditional approval of MOR208 is granted based on L- MIND. Discussions with the FDA regarding the biomarker assay are currently being planned and are expected to take place in the middle of this year. The pre-planned, event-driven interim analysis of B-MIND remains projected to take place in the second half of 2019. Depending on the outcome of the interim analysis, an increase from 330 to 450 patients may be required, in which case an event-driven primary analysis of the study is expected in the first half of 2021.

"Our L-MIND trial continues as planned and we are on track to completing our regulatory submission to the FDA this year", commented Dr. Malte Peters, Chief Development Officer of Morphosys AG. "Further, we are having early conversations with European regulators about the possibility of using L-MIND as the basis for a filing in Europe. We hope to have a clearer picture of the regulatory path in Europe within the next several months. Following discussions with the FDA, we have introduced a co-primary endpoint into the B-MIND trial based on pre-clinical data that suggest the involvement of a certain biomarker. The amended B-MIND trial enables us to test the hypothesis that MOR208 shows enhanced activity in patients who can be identified using the biomarker, while in addition allowing us to test efficacy in the unselected patient population as originally planned."

About CD19 and MOR208
CD19 is broadly and homogeneously expressed across different B cell malignancies including DLBCL and CLL. CD19 has been reported to enhance B cell receptor (BCR) signaling, which is assumed important for B cell survival, making CD19 a potential target in B cell malignancies.
MOR208 is an investigational humanized Fc-engineered monoclonal antibody directed against CD19. Fc-modification of MOR208 is intended to lead to a significant potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), thus aiming to improve a key mechanism of tumor cell killing. MOR208 has been observed in preclinical models to induce direct apoptosis by binding to CD19, which is assumed to be involved in B cell receptor (BCR) signaling.
MorphoSys is clinically investigating MOR208 as a therapeutic option in B cell malignancies in a number of ongoing combination trials. An open-label phase 2 combination trial (L-MIND study) is investigating the safety and efficacy of MOR208 in combination with lenalidomide in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). Based on interim data from L-MIND, in October 2017 the U.S. FDA granted Breakthrough Therapy Designation for MOR208 plus lenalidomide in this patient population. The pivotal phase 2/3 B-MIND study is designed to investigate MOR208 in combination with the chemotherapeutic agent bendamustine in patients with relapsed/refractory DLBCL who are not eligible for high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) in comparison to the combination of the anti-CD20 antibody rituximab plus bendamustine. In addition, MOR208 is currently being investigated in patients with relapsed/refractory CLL/SLL after discontinuation of a prior Bruton tyrosine kinase (BTK) inhibitor therapy (e.g. ibrutinib) in combination with idelalisib or venetoclax.

On March 7, 2019 CASI Pharmaceuticals, Inc. (Nasdaq: CASI), a U.S. based pharmaceutical company with a platform to develop and accelerate the launch of pharmaceutical products and innovative therapeutics in China, U.S., and throughout the world, reported that the National Medical Products Administration (NMPA) has approved the Company’s Clinical Trial Application (CTA) allowing for a registration clinical trial to evaluate the efficacy and safety of vincristine sulfate LIPOSOME injection (MARQIBO) (Press release, CASI Pharmaceuticals, MAR 7, 2019, View Source [SID1234534307]).

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MARQIBO is a U.S. Food and Drug Administration (FDA)-approved product currently marketed in the U.S. by Spectrum Pharmaceuticals, Inc. (Spectrum), for the treatment of adult patients with Philadelphia chromosome–negative (Ph‒) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following two or more anti-leukemia therapies. CASI acquired greater China rights to this drug from Spectrum.

The Company is currently reviewing certain requirements provided by the Center for Drug Evaluation (CDE), a division of the NMPA, and upon satisfying those requirements, the Company will commence the registration trial for MARQIBO.

Wei-Wu He, Ph.D., CASI’s Executive Chairman commented, "Ph negative ALL is a rare but aggressive disease and while patient outcomes have vastly improved over the last three decades, patients continue to relapse and current salvage therapies are inadequate, particularly among the aging Chinese patient population. MARQIBO is the first and only liposome-encapsulated vincristine approved and marketed in the U.S. for second line treatment of adult Philadelphia chromosome-negative acute lymphoblastic leukemia and has been safely administered in patients since its U.S. approval in 2012. Receiving NMPA approval to conduct the registration trial in China with MARQIBO is an important milestone for CASI. This approval, along with the recent CTA approval for ZEVALIN and the fast track market approval of EVOMELA, further demonstrates CASI’s regulatory strength in working with the NMPA to advance products through the approval process."

On March 7, 2019 Geron Corporation (Nasdaq: GERN) reported financial results for the fourth quarter and full year ended December 31, 2018 and recent events (Press release, Geron, MAR 7, 2019, View Source [SID1234534067]). As of year-end 2018, the Company had approximately $182 million in cash and marketable securities, which is sufficient to commence the planned Phase 3 clinical trial of imetelstat in lower risk myelodysplastic syndromes (MDS) by mid-year 2019.

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"We expect 2019 to be a pivotal year," said John A. Scarlett, M.D., Chairman and Chief Executive Officer. "We are making good progress in the transition of the imetelstat program and expect to assume sponsorship of the imetelstat clinical trials by the end of the second quarter. We continue planning to open the Phase 3 clinical trial of imetelstat in lower risk MDS for enrollment by mid-year, as well as evaluating the potential for late-stage development in MF. In addition, we expect to further expand our team with individuals who have strong development expertise that will enable us to build a robust hematology-oncology franchise."

Recent Events

Building a Development Team with Hematology-Oncology Expertise

The Company recently announced the hiring of two key development executives. Aleksandra Rizo, M.D., Ph.D., the former clinical lead for the imetelstat program at Janssen, joined Geron as Chief Medical Officer. Israel Gutierrez, M.D., who has more than 20 years of oncology clinical development experience, joined Geron as Vice President, Pharmacovigilance and Drug Safety. In addition, Geron plans to open an office in northern New Jersey to access experienced personnel with late-stage hematology-oncology clinical drug development expertise, as well as to enable efficient support for global clinical trials, including the Phase 3 clinical trial of imetelstat in lower risk MDS.

Fourth Quarter 2018 Highlights

IMerge Phase 2 Data Presented Support Initiation of Phase 3 Trial in Lower Risk MDS

Data for the Phase 2 portion of IMerge were presented in an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting on December 2, 2018. Geron believes these data support initiating the Phase 3 portion of IMerge to address an unmet medical need for patients for whom erythropoiesis stimulating agents (ESAs) are not effective and for whom currently available therapies show only modest efficacy, especially in patients with high baseline transfusion burdens who are difficult-to-treat. Lower risk MDS patients in the U.S. represent a large unmet need as there has not been a new drug approved by the Food and Drug Administration (FDA) since 2006.

In the Phase 2 portion of IMerge, 38 patients were enrolled who were transfusion dependent with Low or Intermediate-1 risk non-del(5q) MDS who have relapsed after or are refractory to prior treatment with an ESA and naïve to treatment with a hypomethylating agent (HMA) or lenalidomide. In the trial, transfusion dependence is defined as a patient requiring a minimum of four units of red blood cells (RBC) over a consecutive 8-week time period to treat anemia. The median baseline RBC transfusion burden in the Phase 2 portion of IMerge was eight units per eight weeks, ranging from four to 14 units. The primary efficacy endpoint of the trial is the rate of RBC transfusion-independence (RBC TI) lasting at least eight weeks (8-week RBC TI rate), which is defined as the proportion of patients who are transfusion free for at least eight consecutive weeks since entry into the trial. Key secondary endpoints include durability of response as evidenced through 24-week RBC TI rate and breadth of response through reduction in RBC transfusion burden and rate of RBC transfusions, as well as responses across MDS sub-types.

Primary Efficacy Endpoint:

37% (14/38) of patients achieved an 8-week RBC TI rate
Secondary Efficacy Endpoints:

Durability

26% (10/38) of patients achieved a 24-week RBC TI rate
Transfusion Reduction

The rate of hematologic improvement-erythroid (HI-E) was 71% (27/38), as measured by a reduction of at least four RBC units over eight weeks compared with prior transfusion burden
Mean relative reduction of RBC transfusion burden from baseline was 68%
Broad Clinical Activity Observed

Similar 8-week RBC TI rates were observed in patients with baseline serum erythropoietin (sEPO) levels less than or greater than 500mU/mL
8-week RBC TI rates were also consistent between ringed-sideroblast (RS) positive patients and other patients
The ASH (Free ASH Whitepaper) presentation reported data based on a data cut-off date of October 26, 2018. As of the data cut-off date, the median duration of RBC TI had not been reached. Geron expects more mature data from patients continuing on treatment in the Phase 2 portion of IMerge to be available in 2019 and anticipates submitting such data for presentation at a future medical conference.

IMbark Phase 2 Data Presented Suggest Meaningful Survival Outcome in Relapsed/Refractory MF Patients

Data from the Phase 2 IMbark clinical trial, including new overall survival data, were presented in an oral presentation at ASH (Free ASH Whitepaper) on December 3, 2018.

The IMbark trial evaluated two starting dose levels of imetelstat (either 4.7 mg/kg or 9.4 mg/kg administered by intravenous infusion every three weeks) in more than 100 patients with Intermediate-2 or High-risk myelofibrosis (MF) who were relapsed or refractory to janus kinase inhibitor (JAKi) therapy. To be eligible for enrollment in the IMbark trial, patients had to meet rigorous criteria for having failed or not responded to JAKi treatment, including documented progressive disease during or after JAKi therapy. The ASH (Free ASH Whitepaper) presentation highlighted efficacy and safety data from the trial’s primary analysis, as well as overall survival (OS) data with a clinical cutoff of October 22, 2018 and a median follow up of 27 months.

The ASH (Free ASH Whitepaper) presentation reported that the median OS for the 9.4 mg/kg dosing arm was 29.9 months, which suggests a meaningful survival outcome with imetelstat treatment in this poor-prognosis, relapsed/refractory patient population where there are currently no approved treatments today. Other observational studies of similar patient populations at academic medical centers published recently in medical literature have reported median OS ranges of approximately 12 to 14 months after failure of or discontinuation of ruxolitinib, a JAKi.

Geron plans to discuss the potential for late-stage development of imetelstat in MF with current IMbark investigators, other key opinion leaders (KOLs) and regulatory authorities. The Company expects to facilitate KOL discussions over the coming months. Discussions with regulatory authorities are expected to begin after the investigational new drug (IND) sponsorship has been transferred back to Geron.

The Company plans to outline a decision regarding the potential for future late-stage development in MF by the end of the third quarter of 2019. In making this decision, Geron will conduct an assessment of what would be required to achieve clinical and regulatory success, including the cost and duration of any potential clinical trials.

Imetelstat Safety Results

The safety profile reported in both ASH (Free ASH Whitepaper) presentations for imetelstat-treated patients was consistent with prior clinical trials of imetelstat in hematologic malignancies, and no new safety signals were identified. Cytopenias, particularly neutropenia and thrombocytopenia, were the most frequently reported adverse events, which were predictable, manageable and reversible.

Fourth Quarter and Year-End 2018 Results

For the fourth quarter of 2018, the company reported a net loss of $7.3 million, or $0.04 per share, compared to $7.4 million, or $0.05 per share, for the comparable 2017 period. For 2018, the company reported a net loss of $27.0 million, or $0.15 per share, compared to $27.9 million, or $0.18 per share, for 2017.

Revenues for the fourth quarter of 2018 were $375,000 compared to $191,000 for the comparable 2017 period. Revenues for 2018 and 2017 were each $1.1 million and included royalty and license fee revenues under various non-imetelstat license agreements. The Company adopted a new revenue recognition accounting standard as of January 1, 2018 using the modified retrospective transition method. Revenue for 2018 is presented under the new accounting standard, but revenue for 2017 has not been adjusted and continues to be reported under accounting standards used historically. Therefore, there is a lack of comparability between the periods presented. However, the Company does not expect the adoption of the new revenue recognition accounting standard to have a material impact to its financial statements on an ongoing basis.

Total operating expenses for the fourth quarter of 2018 were $10.0 million compared to $8.0 million for the comparable 2017 period. Total operating expenses for 2018 were $32.1 million compared to $30.3 million for 2017.

Research and development expenses for the fourth quarter of 2018 were $5.1 million compared to $2.5 million for the comparable 2017 period. Research and development expenses for 2018 were $13.4 million compared to $11.0 million for 2017. The increase in research and development expenses for the fourth quarter and year-to-date 2018 periods compared to comparable 2017 periods primarily reflects increases in Geron’s share of imetelstat development costs under the former collaboration agreement with Janssen Biotech, Inc. (Janssen) where Geron’s share increased from 50% to 100% as of the termination date of the collaboration agreement and additional costs for the contract research organization (CRO) and other consultants for the transition of the imetelstat program from Janssen to Geron.

General and administrative expenses for the fourth quarter of 2018 were $4.9 million compared to $5.5 million for the comparable 2017 period. General and administrative expenses for 2018 were $18.7 million compared to $19.3 million for 2017. The decrease in general and administrative expenses in 2018 compared to 2017 primarily reflects the net result of reduced personnel related expenses, including lower stock-based compensation expense, partially offset by higher consulting expenses and higher patent legal expenses with the termination of the imetelstat collaboration with Janssen, as imetelstat patent costs previously were being shared by the two companies on a 50/50 basis.

Interest and other income for the fourth quarter of 2018 was $1.1 million compared to $375,000 for the comparable 2017 period. Interest and other income for 2018 was $3.3 million compared to $1.4 million for 2017. The increase in interest and other income for 2018 compared to 2017 primarily reflects higher yields on the Company’s marketable securities portfolio.

Planned 2019 Activities and Milestones

Geron’s plans for 2019 primarily focus on advancing imetelstat development. The Company believes building a development team with hematology-oncology expertise is essential to executing the Phase 3 clinical trial in lower risk MDS and evaluating the potential for late-stage development in MF, as well as in the future, exploring additional indications for imetelstat and being able to pursue other innovative therapeutics in hematology-oncology. Geron expects the following activities and milestones to occur in 2019:

Transition of Imetelstat Development Program

Complete the transfer of the IND back to Geron by the end of the second quarter.

Complete the transfer of the imetelstat clinical development program back to Geron by the end of the third quarter.

Actively recruit highly-experienced personnel with drug development expertise in myeloid malignancies.
MDS Development

Commence screening and enrollment for the Phase 3 portion of IMerge by mid-year.

Present more mature data from patients in the Phase 2 portion of IMerge at a medical conference.
MF Development

Conduct discussions with IMbark investigators, other MF KOLs and regulatory authorities to identify and consider potential late-stage clinical development plans for relapsed/refractory MF patients.

Outline decision regarding the potential for late-stage development of imetelstat in MF by the end of the third quarter.
Projected 2019 Financial Guidance

The Company expects its operating expenses to increase as it assumes full responsibility for the development and potential commercialization of imetelstat. For fiscal year 2019, the Company expects its operating expense burn to range from $65 to $70 million, of which approximately $10 to $15 million represents one-time costs, such as imetelstat program transition activities from Janssen to Geron, including the transfer of the IND sponsorship, and purchase of raw materials and other supplies in preparation for new drug manufacturing. In addition to the one-time costs, projected 2019 operating expense guidance includes costs for the expansion of the internal development team, the global Phase 3 clinical trial in MDS and the opening of the New Jersey office. The Company plans to grow to a total of approximately 30 to 40 employees by year-end 2019, of which half will be research and development personnel.

Conference Call

Geron will host a conference call to discuss fourth quarter and full year financial results and recent events at 4:30 p.m. ET on Thursday, March 7, 2019.

Participants may access the conference call live via telephone by dialing domestically +1 (877) 303-9139 or internationally +1 (760) 536-5195. The conference ID is 6771719. A live, listen-only webcast will also be available on the Company’s website at www.geron.com/investors/events. If you are unable to listen to the live call, an archived webcast will be available on the Company’s website for 30 days.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data suggest imetelstat may have disease-modifying activity through the suppression of malignant progenitor cell clone proliferation, which allows potential recovery of normal hematopoiesis. Ongoing clinical studies of imetelstat include a Phase 2/3 trial called IMerge in lower risk myelodysplastic syndromes (MDS) and a Phase 2 trial called IMbark in Intermediate-2 or High-risk myelofibrosis. Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for the treatment of patients with transfusion-dependent anemia due to lower risk MDS who are non-del(5q) and refractory or resistant to an erythroid stimulating agent.