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Sutro Biopharma Announces Encouraging Interim Phase 1 Safety Data on a Potential First-in-Class Antibody-Drug Conjugate STRO-001 for the Treatment of B-cell Malignancies at the European Hematology Association Congress

On June 15, 2019 Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation oncology therapeutics, reported encouraging interim safety data from an ongoing Phase 1 dose escalation clinical trial of its product candidate STRO-001, a novel, specific and homogeneous anti-CD74 antibody-drug conjugate (ADC), as a potential therapy for patients with B-cell malignancies (Press release, Sutro Biopharma, JUN 15, 2019, View Source [SID1234537101]). The interim data from the trial includes 21 patients and separate dosing cohorts for multiple myeloma (10 MM patients) and non-Hodgkin lymphoma (11 NHL patients), was presented at the 24th European Hematology Association (EHA) (Free EHA Whitepaper) Congress in Amsterdam. The data also showed encouraging preliminary anti-tumor activity for the ADC, including one complete response (CR) and one partial response (PR) among a cohort of heavily pre-treated patients with DLBCL. Overall, STRO-001 was generally well-tolerated.

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"CD74 is expressed on B cells throughout differentiation and appears to be an attractive target for the treatment of non-Hodgkin lymphoma and multiple myeloma," said Dr. Nirav Shah, Assistant Professor of Medicine at Medical College of Wisconsin. "The interim safety results from the early dose escalation cohorts of the STRO-001 Phase 1 clinical trial are encouraging, especially considering the complete response seen in one of our patients."

Bill Newell, Sutro’s Chief Executive Officer added, "There is a continuing need for new treatment options for patients with B-cell malignancies as many patients relapse or become refractory to even the newest treatment regimens. STRO-001 was designed to directly target cancer cells to deliver a cytotoxic payload, an approach that enables greater precision in treating tumors. We view the data as encouraging and believe that STRO-001 can be an important new treatment option to address an unmet need for patients with B-cell malignancies."

The ongoing Phase 1, open-label, multicenter, dose escalation trial of STRO-001 is designed to evaluate the safety, tolerability and preliminary anti-tumor activity of STRO-001 in adults with B-cell malignancies. Based on interim data from the clinical trial through May 14, 2019, STRO-001 has been generally well-tolerated. The most common treatment emergent adverse events included fatigue, nausea, chills and infusion reactions. Neither ocular toxicity signals nor anti-drug antibodies have been observed and the maximum tolerated dose for both dosing cohorts has not been reached.

Sutro’s cell-free protein synthesis and site-specific conjugation (XpressCF+) platform technology was used to discover and develop STRO-001, a CD74-targeting ADC. STRO-001 contains a potent maytansinoid warhead conjugated to two specific sites (drug-to-antibody ratio of 2) using a stable non-cleavable linker. The interim data as of May 14, 2019, included 21 patients across two cohorts: cohort A for MM and cohort B for NHL. The patients enrolled in the trial were generally heavily pre-treated with a median of six lines of prior therapy. STRO-001 was administered as a 60-minute IV infusion on Days 1 and 15 of a 28-day cycle until disease progression or dose limiting toxicity. As of May 14, 2019, the MM cohort was at dose level 0.65 mg/kg and the NHL dose cohort was at 0.91 mg/kg. The trial continues to enroll patients in dose escalation in both MM and NHL cohorts. This trial is registered with clinicaltrials.gov identifier NCT03424603.

Incyte Announces Positive Results from a Phase 2 Study of Ruxolitinib Cream in Patients with Vitiligo

On June 15, 2019 Incyte (Nasdaq:INCY) reported 24-week results from its randomized, double-blind, dose-ranging, vehicle-controlled, Phase 2 study evaluating ruxolitinib cream, a nonsteroidal, anti-inflammatory, JAK inhibitor therapy, in adult patients (18 to 75 years of age) with vitiligo (Press release, Incyte, JUN 15, 2019, View Source [SID1234537100]). The study met its primary endpoint, demonstrating that significantly more patients treated with ruxolitinib cream for 24 weeks achieved a ≥50 percent improvement from baseline in the facial vitiligo area severity index (F-VASI50) score compared to patients treated with a vehicle control (non-medicated cream). F-VASI50 response was most notably achieved with ruxolitinib cream 1.5 percent administered once daily (QD) and twice daily (BID) vs. vehicle control (50 percent and 45 percent vs. 3 percent, respectively; P<0.001).

These results are being presented at the 24thWorld Congress of Dermatology (WCD) in Milan, Italy, during a late-breaking research session today, June 15, 2019, from 9:25 a.m. CET to 9:35 a.m. CET (3:25 a.m. EDT to 3:35 a.m. EDT). (Location: Room Yellow 3).

"The positive 24-week data presented at the World Congress of Dermatology support the potential of ruxolitinib cream to offer a novel treatment option for patients with this chronic autoimmune disease," said Steven Stein, M.D., Chief Medical Officer, Incyte. "For patients who choose to seek treatment for their vitiligo, current options are often limited by inadequate efficacy or potential side effects. We look forward to advancing ruxolitinib cream into Phase 3 development for vitiligo in the hope that it may become the first approved treatment for what can be a life-altering disease."

Key 24-week results include:

Significantly more patients achieved F-VASI50 after 24 weeks of treatment with all ruxolitinib cream regimens compared to the vehicle control. The highest F-VASI50 response was achieved with ruxolitinib cream 1.5 percent QD and BID compared to vehicle control (50 percent and 45 percent vs. 3 percent, respectively; P<0.001).
A ≥75 percent improvement from baseline in the facial vitiligo area severity index score was achieved by 17 percent, 30 percent, and 0 patients treated with ruxolitinib cream 1.5 percent QD, BID, and vehicle cream, respectively.
Facial Physician Global Vitiligo Assessment (F-PhGVA) scores of clear (no signs of vitiligo) or almost clear (only specks of depigmentation present) skin were achieved by 13 percent, 9 percent, and 0 patients receiving ruxolitinib cream 1.5 percent QD, BID, and vehicle cream, respectively.
Ruxolitinib cream was generally well-tolerated at all dosage strengths.
Over-activity of the JAK signaling pathway has been shown to drive inflammation involved in the pathogenesis and progression of vitiligo. These data on ruxolitinib cream, a JAK inhibitor, support the planned initiation of pivotal Phase 3 development later in 2019, for which preparations are already underway.

"As a physician, I am looking for safe and effective options that may help my patients achieve their treatment goals," said David Rosmarin, M.D., Assistant Professor at the Tufts University School of Medicine. "I am encouraged by these clinical trial results and the potential of ruxolitinib cream to become an important treatment option for the repigmentation of vitiligo lesions."

About Vitiligo

Vitiligo is a chronic, immune-mediated skin disease that is estimated to affect between 2 and 3 million people in the U.S. and for which there is no known cure. It can occur at any age, although many people experience vitiligo symptoms before the age of 20.

Vitiligo is characterized by the progressive loss of pigmentation in patches of skin across the body, causing the skin to appear lighter. This occurs when pigment-producing cells known as melanocytes are destroyed or stop functioning. Vitiligo can affect any area of skin on the body and may also affect hair, eyes or the inside of the mouth. The exact cause of vitiligo is unknown, though recent research suggests that changes in the immune system may be responsible for the disease.

About the Study

The safety and efficacy of ruxolitinib cream were evaluated in an Incyte-sponsored randomized, double-blind, dose-ranging, vehicle-controlled, Phase 2 study (NCT03099304), which began in April 2017. The Phase 2 study program is comprised of three parts spanning 104 weeks. The first part of the study – the findings for which are being presented at the 24th WCD – spanned 24 weeks and enrolled 157 adults (aged 18-75 years) diagnosed with vitiligo and with depigmented areas of at least 0.5 percent of the body surface area (BSA) on the face and at least 3 percent of the total BSA on nonfacial areas.

Patients were equally randomized across five treatment arms, including: ruxolitinib cream 1.5 percent, 0.5 percent or 0.15 percent administered QD; ruxolitinib cream 1.5 percent administered BID; or vehicle control for 24 weeks.

The primary efficacy endpoint was the percentage of patients treated with ruxolitinib cream who achieved F-VASI50 score at Week 24, compared to patients treated with vehicle control. Key secondary endpoints included the proportion of patients who achieved a F-PhGVA score of 0 or 1 at Week 24 and the safety and tolerability of ruxolitinib cream.

For more information about the study, please visit: View Source

About Ruxolitinib Cream

Ruxolitinib cream is a proprietary formulation of Incyte’s selective JAK1/JAK2 inhibitor ruxolitinib that has been designed for topical application. Ruxolitinib cream is currently in Phase 3 development for the treatment of patients with mild to moderate atopic dermatitis (TRuE-AD) with results expected in the first half of 2020, and is expected to enter Phase 3 development for the treatment of certain patients with vitiligo (TRuE-V) in the second half of 2019. Incyte has worldwide rights for the development and commercialization of ruxolitinib cream.

Conference Call Information

Incyte will host an investor conference call and webcast at 8:00 a.m. EDT on Monday, June 17, 2019—the call and webcast can be accessed via the Events and Presentations tab of the Investor section of www.incyte.com.

To access the conference call on Monday, June 17, 2019, please dial 877-407-3042 for domestic callers or +1-201-389-0864 for international callers. When prompted, provide the conference identification number, 13689599.

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, 13689599.

Calquence significantly prolonged the time patients lived without disease progression in relapsed or refractory chronic lymphocytic leukaemia

On June 15, 2019 AstraZeneca reported detailed results from the interim analysis of the Phase III ASCEND trial at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress in Amsterdam, showing Calquence (acalabrutinib) significantly prolonged the time patients live without disease progression in relapsed or refractory chronic lymphocytic leukaemia (CLL) (Press release, AstraZeneca, JUN 15, 2019, View Source [SID1234537099]).

The ASCEND trial compared Calquence with the physician’s choice of rituximab combined with idelalisib (IdR) or bendamustine (BR) in patients with relapsed or refractory CLL.

At a median follow-up of 16.1 months, results from the trial showed a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) for patients treated with Calquence vs. IdR or BR, reducing the risk of disease progression or death by 69% (HR, 0.31; 95% CI, 0.20-0.49, p<0.0001). The median time without disease progression for patients treated with Calquence has not yet been reached vs. 16.5 months in the control arm. At 12 months, 88% of patients on Calquence showed no disease progression compared to 68% for the control arm. The safety and tolerability of Calquence was consistent with its established profile.

José Baselga, Executive Vice President, Oncology R&D said: "These data add to the growing body of evidence to support the profile of Calquence as a selective BTK inhibitor that offers a chemotherapy-free treatment option with a favourable safety profile in chronic lymphocytic leukaemia, a life-threatening disease. These data, along with our recent positive results from the Phase III ELEVATE-TN trial in previously-untreated chronic lymphocytic leukaemia, will serve as the foundation for regulatory submissions later this year."

Paolo Ghia, MD, Professor, Medical Oncology, Università Vita-Salute San Raffaele in Milan, and investigator of the ASCEND trial, said: "This is the first randomised trial to directly compare a BTK inhibitor as monotherapy with standard chemoimmunotherapy or idelalisib and rituximab combinations. With a significant improvement in progression-free survival and a favourable safety profile, acalabrutinib may become an important choice for the treatment of patients with relapsed or refractory chronic lymphocytic leukaemia."

Kaplan-Meier plot for PFS as assessed by an independent review committee in the intent-to-treat population1

calquence
Calquence (arm A) vs IdR or BR (arm B)

Calquence
*Secondary primary malignancy **Non-melanoma skin cancer.

AstraZeneca recently announced that the Phase III ELEVATE-TN trial met its primary endpoint at interim analysis in patients with previously-untreated CLL and that full results will be reported at a forthcoming medical meeting. Calquence is currently approved for the treatment of adults with relapsed or refractory mantle cell lymphoma (MCL) in the US, Brazil, the United Arab Emirates, and Qatar and is being developed for the treatment of CLL and other blood cancers.

About ASCEND

ASCEND (ACE-CL-309) is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy of Calquence in previously-treated patients with CLL.2 In the trial, 310 patients were randomised (1:1) into two arms. Patients in the first arm received Calquence monotherapy (100mg twice daily until disease progression). Patients in the second arm received physician’s choice of either rituximab in combination with idelalisib or rituximab in combination with bendamustine.1,2

The primary endpoint is PFS assessed by an independent review committee (IRC), and key secondary endpoints include physician-assessed PFS, IRC- and physician-assessed overall response rate (ORR) and duration of response (DoR), as well as overall survival (OS), patient reported outcomes (PROs) and time to next treatment (TTNT).1,2

About Calquence

Calquence (acalabrutinib) was granted accelerated approval by the US Food and Drug Administration (FDA) in October 2017 for the treatment of adult patients with MCL who have received at least one prior therapy. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Calquence is an inhibitor of Bruton tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.3 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.

As part of an extensive clinical development programme, AstraZeneca and Acerta Pharma are currently evaluating Calquence in 26 company-sponsored clinical trials. Calquence is being developed for the treatment of multiple B-cell blood cancers including CLL, MCL, diffuse large B-cell lymphoma, Waldenstrom macroglobulinaemia, follicular lymphoma, and multiple myeloma and other haematologic malignancies. Beyond the positive Phase III trials ASCEND and ELEVATE-TN, other Phase III trials in CLL are ongoing, including ELEVATE-RR (ACE-CL-006) evaluating acalabrutinib vs. ibrutinib in patients with previously-treated high-risk CLL, and ACE-CL-311 evaluating acalabrutinib in combination with venetoclax and with/without obinutuzumab in patients with previously-untreated CLL without 17p deletion or TP53 mutation.

About chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in adults, with an estimated 191,000 new cases globally and 20,720 new cases in the US annually, and prevalence that is expected to grow with improved treatment.4-7 In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections.4 As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells and platelets.4 This could result in anaemia, infection and bleeding.4 B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.

About AstraZeneca in haematology

Leveraging its strength in oncology, AstraZeneca has established haematology as one of four key oncology disease areas of focus. The Company’s haematology franchise includes two US FDA-approved medicines and a robust global development programme for a broad portfolio of potential blood cancer treatments. Acerta Pharma serves as AstraZeneca’s haematology research and development arm. AstraZeneca partners with like-minded science-led companies to advance the discovery and development of therapies to address unmet need.

In October 2018, AstraZeneca and Innate Pharma announced a global strategic collaboration that included Innate Pharma licensing the US commercial rights of Lumoxiti (moxetumomab pasudotox-tdfk), and with support from AstraZeneca, will continue EU development and commercialisation, pending regulatory submission and approval.

About AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines

Tolero Pharmaceuticals Presents Clinical Data from Ongoing Phase 1 Zella 101 Study Evaluating Investigational Agent Alvocidib in Combination with Cytarabine and Daunorubicin in Patients with Newly Diagnosed AML at EHA 2019

On June 14, 2019 Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, reported data for the first time from the ongoing Phase 1 Zella 101 study evaluating the safety and clinical activity of alvocidib, a potent CDK9 inhibitor, in combination with cytarabine and daunorubicin in patients with newly diagnosed acute myeloid leukemia (AML) (Press release, Tolero Pharmaceuticals, JUN 14, 2019, View Source [SID1234537097]). These results were presented in a poster presentation at the 24th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper), being held June 13-16, 2019 in Amsterdam, The Netherlands.

Preliminary data from the study indicated that alvocidib in combination with cytarabine and daunorubicin has shown clinical activity with acceptable safety in patients with newly diagnosed AML. Of the 18 evaluable patients, more than three-quarters (78%, n=14) achieved a complete remission (CR) or complete remission with incomplete hematologic recovery (CRi). Of these patients attaining a CR/CRi, 78% (n=11) reached the 30-day post-study evaluation, per the study protocol. A subset of these patients, 27% (n=3 of 11) proceeded to stem cell transplant. Additionally, among adverse cytogenic risk patients (n=9) who generally respond poorly to induction therapy, two-thirds (67%, n=6 of 9), achieved a CR/CRi.1

Of the patients that attained a CR/CRi (n=14), 10 (71%) are still in remission with a median follow-up of 76 days. In addition, 21 of 22 (95%) enrolled patients are still alive, with a median follow-up of 70 days.

Adverse events (AEs) in the study include diarrhea, tumor lysis syndrome, infections and elevated AST levels and were consistent with those noted in previous alvocidib studies.1

"These preliminary data from the Zella 101 study in patients with newly diagnosed AML are encouraging, as they add to the growing body of evidence from the alvocidib clinical program," said David J. Bearss, Ph.D., Chief Executive Officer of Tolero Pharmaceuticals. "We look forward to continuing this study to further our understanding of how the combination of alvocidib with cytarabine and daunorubicin may benefit this patient population."

Additional data from Tolero’s pipeline will also be presented in an oral presentation at the meeting, highlighting the impact of investigational agent TP-0903, an oral AXL receptor tyrosine kinase (RTK) inhibitor, on Axl-RTK inhibition in patients with several tumors, including chronic lymphocytic leukemia (CLL).

Below are the details for the presentations:

Abstract Title

Details

Zella 101: Phase 1 Study of Alvocidib
Followed by 7+3 Induction in Newly
Diagnosed AML Patients

Abstract # PF285

June 14, 5:30-7 p.m. CEST

Poster Presentation

AXL-RTK Inhibition Directs the
Functional Phenotype of Chimeric
Antigen Receptor T Cells

Abstract # S909

June 15, 4-4:15 p.m. CEST

Oral Presentation

About Alvocidib
Alvocidib is an investigational small molecule inhibitor of cyclin-dependent kinase 9 (CDK9) currently being evaluated in a Phase II study, Zella 201, in patients with relapsed or refractory MCL-1 dependent acute myeloid leukemia, AML, in combination with cytarabine and mitoxantrone (NCT02520011). Alvocidib is also being evaluated in Zella 101, a Phase I clinical study evaluating the maximum tolerated dose, safety and clinical activity of alvocidib in combination with (7+3) in newly diagnosed patients with AML (NCT03298984), and Zella 102, a Phase 1b/2 study in patients with myelodysplastic syndromes, MDS, in combination with decitabine (NCT03593915). In addition, alvocidib is being evaluated in a Phase 1 study in patients with relapsed or refractory AML in combination with venetoclax (NCT03441555).

About CDK9 Inhibition and MCL-1
MCL-1 is a member of the apoptosis-regulating BCL-2 family of proteins.2 In normal function, it is essential for early embryonic development and for the survival of multiple cell lineages, including lymphocytes and hematopoietic stem cells.3 In MCL-1–dependent AML, MCL-1 inhibits apoptosis and sustains the survival of leukemic blasts, which may lead to relapse or resistance to treatment.2,4 The expression of MCL-1 in leukemic blasts is regulated by cyclin-dependent kinase 9 (CDK9).5,6 Because of the short half-life of MCL-1 (2-4 hours), the effects of targeting upstream pathways are expected to reduce MCL-1 levels rapidly.5 Inhibition of CDK9 has been shown to block MCL-1 transcription, resulting in the rapid downregulation of MCL-1 protein, thus restoring the normal apoptotic regulation.2

Ampio Pharmaceuticals, Inc. Announces Proposed Public Offering of Common Stock

On June 14, 2019 Ampio Pharmaceuticals, Inc. (NYSE American: AMPE) ("Ampio"), reported that it intends to offer and sell shares of its common stock in an underwritten public offering (Press release, Ampio, JUN 14, 2019, View Source [SID1234537096]). Ampio expects to grant the underwriters a 45-day option to purchase additional shares of common stock offered in the public offering. The offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

Ampio intends to use the net proceeds from the proposed offering for working capital and general corporate purposes, including funding for its clinical trial (AP-013).

ThinkEquity, a division of Fordham Financial Management, Inc., is acting as sole book-running manager for the offering.

A shelf registration statement on Form S-3 (File No. 333-217094) relating to the shares of common stock to be issued in the proposed offering was filed with the Securities and Exchange Commission (SEC) and is effective. This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

A preliminary prospectus supplement and accompanying prospectus describing the terms of the proposed offering will be filed with the SEC. The securities may be offered only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. Copies of the preliminary prospectus supplement and the accompanying prospectus relating to the securities being offered may also be obtained from ThinkEquity, a division of Fordham Financial Management, Inc., 17 State Street, 22nd Floor, New York, New York 10004, by telephone at (877) 436-3673, by email at [email protected]. Electronic copies of the preliminary prospectus supplement and accompanying prospectus will also be available on the SEC’s website at View Source

Safe Harbor

This press release contains forward-looking statements regarding the proposed public offering and the intended use of proceeds from the offering. The offering is subject to market and other conditions and there can be no assurance as to whether or when the offering may be completed or as to the actual size or terms of the offering. Forward-looking statements involve known and unknown risks, uncertainties and other factors that could cause actual results to differ materially, including those risks disclosed in under the caption "Risk Factors" in the preliminary prospectus supplement related to the offering and our Annual Report on Form 10-K filed with the SEC on March 18, 2019, our Quarterly Report on Form 10-Q filed with the SEC on May 10, 2019 and our other filings with the SEC. Ampio Pharmaceutcials, Inc. cautions readers not to place undue reliance on any forward-looking statements and it does not undertake, and specifically disclaims any obligation, to update