On February 24, 2020 Nymox Pharmaceutical Corporation (NASDAQ: NYMX) is reported that a new peer review report was published in the World Journal of Urology, documenting the successful long-term clinical trial results after Fexapotide Triflutate treatment for early stage prostate cancer (Press release, Nymox, FEB 24, 2020, View Source [SID1234554649]).

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This report represents the first publication in the medical literature of multi-year long-term data from a well-powered prospective randomized multi-center clinical trial for a prostate injectable treatment in men targeted to low grade early prostate cancer and showing statistically significant efficacy for a locally targeted molecular injectable treatment.

The new publication is entitled "Prospective Evaluation of Fexapotide Triflutate Injection ‎Treatment of Grade Group 1 Prostate Cancer: Four Year Results". The authors are Neal Shore, Myrtle Beach, SC; Steven A. Kaplan, New York, NY; Ronald Tutrone, Baltimore, MD; Richard Levin, Towson, MD; James Bailen, Louisville, KY; Alan Hay, Salem, OR; Susan Kalota, Tucson, AZ; Mohamed Bidair, San Diego, CA; Sheldon Freedman, Las Vegas, NV; Kenneth Goldberg, Lewisville, TX; Frederick Snoy, Albuquerque, NM; Jonathan I. Epstein, Baltimore, MD. The article is available online at View Source

The Fexapotide (FT) study was started in 2012 and enrolled 147 men with localized Gleason Grade 6 T1c prostate cancer at 28 U.S. clinical investigation sites. Patients were followed with clinical and laboratory evaluations and regular periodic prostate biopsies for up to 5 years. Patients randomized to FT were treated with a single one-time targeted injection of FT, either 2.5mg or 15mg. Statistical comparisons were made over time of the proportions of subjects and untreated controls who progressed to higher Gleason grade and/or invasive treatments instituted with prostatectomy, radiotherapy, or chemotherapy. Important clinical highlights from the study include: FT treatment reduced cancer progression (-67.7%) compared to controls (3 years, FT 15mg, p<.02, pooled FT p=.0265) and also reduced (-54.7%) the incidence of surgery, radiotherapy or chemotherapy (4 years, FT 15mg p<.02; pooled FT p=.0374). At 4 years the incidence of surgery, radiotherapy or chemotherapy with increased Gleason grade was significantly reduced (FT 15mg -73.3% p=.0059, pooled FT p=.0064). Results for the high dose (FT 15mg) were superior to the lower dose (FT 2.5mg). Safety data showed no serious adverse events related to FT during the study.

The current recommended standard of care for these patients is active surveillance: patients are monitored carefully over time to determine if and when the cancer becomes more advanced and thus will require more aggressive treatment, like radiation therapy or surgery.

Dr. Neal Shore, lead author of the report, said "The study results demonstrate data in a large multi-center clinical trial of men treated with transrectal ultrasound guided FT for early stage, low risk prostate cancers, which suggest an effective result for reducing histopathologic progression, as evidenced by repeated biopsies over time, while also demonstrating a favorable safety profile. This study presents long-term FT data which supports its efficacy for avoidance of biologic progression in an active surveillance prostate cancer population. A therapy to optimize the success of an active surveillance strategy is a welcomed advance for these patients."

Dr Steven Kaplan, Professor of Urology and Director of the Benign Urologic Diseases and The Men’s Health Program at Icahn School of Medicine at Mount Sinai, New York, and a co-author of the report said, "This study reports the long-term data from a prospective study of an injectable for localized Grade Group 1 prostate cancer — which is the first time this has been accomplished for a very common problem in men. Regulatory approval of Fexapotide Triflutate (FT) will be a very important treatment adjunct for countless men with this problem."

The FT treatments were administered in a urology office setting without anesthesia or sedation, consisting of a single relatively painless transrectal injection into the area of the prostate cancer. The percentage of patients with surgery or radiotherapy with Gleason grade progression was reduced by 73.3% in patients treated with a single injection of FT 15mg and by 62.6% in pooled (high and low dose FT groups combined) FT patients compared to controls.

Dr. Jonathan Epstein a co-author and researcher involved in the study, stated "Although more and more men are electing active surveillance for low grade prostate cancer, approximately 25-35% will show increased grade on follow-up biopsy which typically leads to definitive therapy. In this study, Fexapotide Triflutate decreased the risk of upgrading on follow-up biopsy enabling men to stay on active surveillance. Even if Fexapotide Triflutate enables men to stay on active surveillance longer before they eventually experience upgrading, there would be a significant benefit for men to delay the onset of side effects associated with therapy and in the interim enjoy a better quality of life. Future studies are needed to expand the criteria for study of Fexapotide Triflutate to include men with large volume Grade Group 1 disease and possibly men with low volume, low percent pattern 4 Grade Group 2 cancer. Identifying the ideal candidates for Fexapotide Triflutate also factoring in multiparametric MRI findings remains to be determined."

FT is a pro-apoptotic proprietary drug which promotes natural programmed cell death (apoptosis) in prostatic glandular cells which compose the prostate cancer. FT has been safely administered to men in clinical trials in the U.S. involving over 1700 patients and controls treated for BPH or prostate cancer. FT has completed Phase 3 studies for BPH and further studies of FT for prostate cancer are planned in the near future.

For further detailed information about the published study please refer to the new report online at the World Journal of Urology.

On February 24, 2020 AbbVie Inc. (NYSE:ABBV) ("AbbVie") reported the extension of the expiration date of the offers to exchange (each, an "Exchange Offer" and, collectively, the "Exchange Offers") any and all outstanding notes of certain series issued by Allergan Finance, LLC ("Allergan Finance"), Allergan, Inc. ("Allergan Inc"), Allergan Sales, LLC ("Allergan Sales") and Allergan Funding SCS ("Allergan Funding" and, together with Allergan Finance, Allergan Inc and Allergan Sales, "Allergan") (the "Allergan Notes") for new notes to be issued by AbbVie (the "AbbVie Notes") and the related consent solicitations (each, a "Consent Solicitation" and, collectively, the "Consent Solicitations") being made by AbbVie on behalf of Allergan to adopt certain amendments to each of the indentures (each, an "Allergan Indenture") governing the Allergan Notes (Press release, AbbVie, FEB 24, 2020, View Source [SID1234554648]). AbbVie hereby extends such expiration date from 5:00 p.m., New York City time, on February 28, 2020 to 5:00 p.m., New York City time, on March 13, 2020 (as the same may be further extended, the "Expiration Date").

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On the early participation date of November 7, 2019, requisite consents were received and supplemental indentures were executed eliminating substantially all of the covenants, restrictive provisions, events of default and any guarantees of the related Allergan Notes in each Allergan Indenture. Such supplemental indentures will become operative only upon settlement of the Exchange Offers.

The Exchange Offers and Consent Solicitations were commenced in connection with AbbVie’s previously announced proposed acquisition of Allergan plc (the "Acquisition") and are being made pursuant to the terms and subject to the conditions set forth in the confidential offering memorandum and consent solicitation statement, dated October 25, 2019, and the related letter of transmittal, each as amended by the press releases dated November 18, 2019, December 20, 2019 and January 27, 2020 and as amended hereby (collectively, the "Offering Documents"), and are conditioned upon the closing of the Acquisition, which condition may not be waived by AbbVie, and certain other conditions that may be waived by AbbVie.

The settlement date for the Exchange Offers is expected to occur promptly after the Expiration Date and the Expiration Date of each of the Exchange Offers is expected to be extended to occur on or about the closing date of the Acquisition. As a result, the Expiration Date may be further extended one or more times. AbbVie currently anticipates providing notice of any such extension in advance of the Expiration Date.

Except as described in this press release, all other terms of the Exchange Offers and Consent Solicitations remain unchanged.

As of 5:00 p.m., New York City time, on February 21, 2020, the principal amounts of Allergan Notes set forth in the table below were validly tendered and not validly withdrawn:

Documents relating to the Exchange Offers and Consent Solicitations will only be distributed to eligible holders of Allergan Notes who complete and return an eligibility form confirming that they are either a "qualified institutional buyer" as defined in Rule 144A under the Securities Act of 1933, as amended (the "Securities Act"), or not a "U.S. person" and outside the United States within the meaning of Regulation S under the Securities Act. Except as amended by the press releases dated November 18, 2019, December 20, 2019 and January 27, 2020 and as amended hereby, the complete terms and conditions of the Exchange Offers and Consent Solicitations are described in the Offering Documents, copies of which may be obtained by contacting Global Bondholder Services Corporation, the exchange agent and information agent in connection with the Exchange Offers and Consent Solicitations, at (866) 470-3900 (U.S. toll-free) or (212) 430-3774 (banks and brokers). The eligibility form is available electronically at: View Source

This news release does not constitute an offer to sell or purchase, or a solicitation of an offer to sell or purchase, or the solicitation of tenders or consents with respect to, any security. No offer, solicitation, purchase or sale will be made in any jurisdiction in which such an offer, solicitation or sale would be unlawful. The Exchange Offers and Consent Solicitations are being made solely pursuant to the Offering Documents and only to such persons and in such jurisdictions as are permitted under applicable law.

The AbbVie Notes offered in the Exchange Offers have not been registered under the Securities Act or any state securities laws. Therefore, the AbbVie Notes may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements of the Securities Act and any applicable state securities laws.

On February 24, 2020 Kitov Pharma Ltd. ("Kitov") (NASDAQ/TASE: KTOV), a clinical-stage company advancing first-in-class therapies to overcome tumor immune evasion and drug resistance, reported it will expand the planned Phase 1/2 clinical trial of NT-219 with cetuximab trial in patients with recurrent or metastatic head and neck cancer, to also include evaluation of NT-219 as monotherapy treatment in patients with advanced solid tumors (Press release, Kitov Pharmaceuticals , FEB 24, 2020, View Source [SID1234554647]). Kitov expects to initiate this study in the second quarter of 2020, pending clearance of its Investigational New Drug application by the U.S. Food and Drug Administration. NT-219 is a small molecule dual inhibitor of IRS1/2 and STAT3, pathways associated with treatment resistance.

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The details of the planned Phase 1/2 trial will be presented in a poster at the 2020 Multidisciplinary Head and Neck Cancers Symposium, which is being held in Scottsdale, Arizona, from February 27-29, 2020. The presentation will include details of the Phase 1/2 study, as well as new preclinical data demonstrating the anti-tumor activity of NT-219 as both a monotherapy and in combination with cetuximab, an epithelial growth factor receptor (EGFR) blocking monoclonal antibody.

"Our strategic decision to expand our planned clinical study to evaluate NT-219 as monotherapy is based on the significant compelling preclinical evidence generated in various studies with NT-219, including the data we will be presenting this week," said Isaac Israel, chief executive officer of Kitov. "The promising preclinical data demonstrate the anti-cancer potential of NT-219, both as a monotherapy and in combination with cetuximab, anti-PD1 inhibitors and other agents. We expect that the establishment of standalone safety data and potential efficacy will provide a solid foundation for further evaluation of NT-219 in a number of different clinical settings. We look forward to advancing NT-219 into the clinic in the second quarter of this year."

The Phase 1/2 study will be an open-label, dose escalation and subsequent expansion phase study. The study will have a dose escalation component of NT-219 as a single agent; a dose escalation phase of NT-219 in combination with cetuximab; and an expansion phase of NT-219 at its recommended Phase 2 level in combination with a standard dose of cetuximab. Advanced solid tumors, as well as recurrent or metastatic squamous cell carcinoma of the head and neck, will be evaluated. Other possible expansion cohorts will be determined based on the Phase 1 dose escalation and further preclinical data.

The primary objectives of the study will be to assess plasma pharmacokinetics, safety, tolerability and maximum tolerated dose of NT219 as a single agent, and in combination with cetuximab. The secondary objectives will be to assess pharmacokinetics and efficacy of different dose levels of NT219, alone and in combination with cetuximab.

Presentation details are as follows:

Abstract Title: A Phase 1/2, Open-Label, Dose Escalation Followed by Single-Arm Expansion to Assess the Safety and Efficacy of NT219 in Combination with Cetuximab in Patients with Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC)

Date: February 27-29, 2020
Presentation number: 312
Session: Poster
Location: Exhibit Hall

The poster will also be available for download from February 27, 2020 at: View Source

On February 24, 2020 GlaxoSmithKline plc reported that the U.S. Food and Drug Administration (FDA) accepted the company’s submission of a supplemental New Drug Application (sNDA) seeking approval of Zejula (niraparib) as a maintenance treatment in the first-line setting for women with advanced ovarian cancer who responded to platinum-based chemotherapy regardless of biomarker status (Press release, GlaxoSmithKline, FEB 24, 2020, View Source [SID1234554646]). The FDA is reviewing the sNDA under the Real-Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.

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The application is supported by data from the PRIMA study (ENGOT-OV26/GOG-3012), which demonstrated clinically-meaningful outcomes of niraparib treatment in the first-line maintenance setting.[1] Results from the PRIMA study were presented at the 2019 European Society for Medical Oncology Congress and simultaneously published in the New England Journal of Medicine. The PRIMA study enrolled women who responded to first-line treatment with platinum-based chemotherapy, including those at higher risk of disease progression, a population previously under-represented in first-line ovarian cancer studies.

In the U.S., ovarian cancer impacts nearly 222,000 women annually,[2] and approximately 85% of women with advanced ovarian cancer will see their disease return.[3] With each recurrence, the time a woman may spend without her cancer progressing until the next recurrence gets shorter.

Zejula is currently approved in the U.S. as a maintenance treatment for women with recurrent ovarian cancer who are in response to platinum-based chemotherapy regardless of BRCA mutation status. It is also approved as a treatment for women with advanced ovarian cancer, following three or more chemotherapy regimens.

About PRIMA
PRIMA is a double-blind, randomised Phase III study designed to evaluate niraparib versus placebo in women being treated first-line for Stage III or IV ovarian cancer. The study assessed the efficacy of niraparib as maintenance therapy, as measured by progression free survival. Patients in complete or partial response to first-line platinum-based chemotherapy were randomised 2:1 to niraparib or placebo.

About Ovarian Cancer
Approximately 22,000 women are diagnosed each year with ovarian cancer in the U.S. Ovarian cancer is the fifth most frequent cause of cancer death among women.[4] Despite high response rates to platinum-based chemotherapy in the first-line, approximately 85% of patients will experience disease recurrence. Once the disease recurs, it is rarely curable with decreasing time intervals to each subsequent recurrence.

About Zejula (niraparib)
Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in multiple pivotal trials. GSK is building a robust niraparib clinical development programme by assessing activity across multiple tumour types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development programme for niraparib includes several combination studies, including a Phase III study as a first-line triplet maintenance treatment in ovarian cancer (FIRST). There is also a Phase II study of niraparib combined with bevacizumab maintenance treatment in advanced ovarian cancer (OVARIO); a Phase II study of niraparib plus dostarlimab in patients with platinum resistant ovarian cancer (MOONSTONE); and a separate study with niraparib in combination with pembrolizumab in patients with triple-negative breast cancer or ovarian cancer (TOPACIO).

Important Safety Information for ZEJULA
Indications

ZEJULA is indicated:

for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.
for the treatment of adult patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:
a deleterious or suspected deleterious BRCA mutation, or
genomic instability and who have progressed more than six months after response to the last platinum-based chemotherapy.
Select patients for therapy based on an FDA-approved companion diagnostic for ZEJULA.

Important Safety Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML), including some fatal cases, was reported in 14 patients (0.7%) out of 1902 patients treated with ZEJULA in clinical trials. The duration of therapy in patients who developed secondary MDS/cancer therapy-related AML varied from less than 2 months to greater than 4 years. These patients had received prior chemotherapy with platinum agents and/or other DNA-damaging agents including radiotherapy. Discontinue ZEJULA if MDS/AML is confirmed.

Hematologic adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported in patients receiving ZEJULA. Grade ≥3 thrombocytopenia, anemia and neutropenia were reported, respectively, in 29%, 25%, and 20% of patients receiving ZEJULA in NOVA, and 28%, 27%, and 13% of patients receiving ZEJULA in QUADRA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 3%, 1%, and 2% of patients in NOVA, and 4%, 2%, and 1% of patients in QUADRA. Do not start ZEJULA until patients have recovered from hematological toxicity caused by prior chemotherapy (≤ Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months, and periodically thereafter. If hematological toxicities do not resolve within 28 days following interruption, discontinue ZEJULA, and refer the patient to a hematologist for further investigations.

Hypertension and hypertensive crisis have been reported in patients receiving ZEJULA. Grade 3-4 hypertension occurred in 9% of patients receiving ZEJULA vs 2% of patients receiving placebo in NOVA, with discontinuation occurring in <1% of patients. Grade 3-4 hypertension occurred in 5% of ZEJULA-treated patients in QUADRA, with discontinuation occurring in <0.2% of patients. Monitor blood pressure and heart rate at least weekly for the first two months, then monthly for the first year, and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Manage hypertension with antihypertensive medications and adjustment of the ZEJULA dose, if necessary.

Embryo-Fetal Toxicity and Lactation: Based on its mechanism of action, ZEJULA can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months after receiving their final dose of ZEJULA. Because of the potential for serious adverse reactions from ZEJULA in breastfed infants, advise lactating women to not breastfeed during treatment with ZEJULA and for 1 month after receiving the final dose.

The most common adverse reactions in >10% of 830 patients who received ZEJULA in NOVA and QUADRA (n = 830) were nausea (70%), fatigue (58%), thrombocytopenia (56%), anemia (50%), vomiting (40%), constipation (38%), abdominal pain (35%), musculoskeletal pain (34%), decreased appetite (26%), neutropenia (25%), insomnia (23%), headache (22%), dyspnea (21%), diarrhea (18%), hypertension (16%), cough (15%), dizziness (13%), hypomagnesemia (13%), urinary tract infection (13%), acute kidney injury (13%), and white blood cell count decreased (11%).

Common lab abnormalities (Grades 1-4) in ≥25% of patients who received ZEJULA in NOVA included: decrease in hemoglobin (85%), decrease in platelet count (72%), decrease in white blood cell count (66%), decrease in absolute neutrophil count (53%), increase in AST (36%) and increase in ALT (28%).

Common lab abnormalities (Grades 1-4) in ≥25% of patients who received ZEJULA in QUADRA included: decreased hemoglobin (83%), increased glucose (66%), decreased platelets (60%), decreased lymphocytes (57%), decreased leukocytes (53%), decreased magnesium (46%), increased alkaline phosphatase (40%), increased gamma glutamyl transferase (40%), increased creatinine (36%), decreased sodium (34%), decreased neutrophils (34%), increased aspartate aminotransferase (29%), and decreased albumin (27%).

GSK in Oncology
GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

On February 24, 2020 Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of immune reset to more patients, reported the completion of dosing in its Phase 1 trial of stem cell mobilization therapy clinical candidate, MGTA-145, as well as updated clinical data from the trial at the Transplant and Cellular Therapy (TCT) Annual Meeting in Orlando, Florida (Press release, Magenta Therapeutics, FEB 24, 2020, View Source [SID1234554644]).

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Mobilized peripheral blood is used for the majority of the 65,000 stem cell transplants performed each year across the United States and Europe, but the current standard of care, G-CSF, requires at least five days of dosing and is associated with significant side effects, including bone pain that often requires narcotics. Further, patients with autoimmune diseases or sickle cell disease can have severe side effects with G-CSF, including potentially fatal complications.

Magenta is developing MGTA-145 as the new first-line standard of care for stem cell mobilization in a broad range of diseases, including autoimmune diseases, blood cancers and genetic diseases. MGTA-145, a CXCR2 agonist, works in combination with plerixafor, a CXCR4 antagonist, to harness the physiological mechanism of stem cell mobilization.

"Current options for stem cell mobilization for transplant are inefficient and cannot be used in all patients. MGTA-145 is a novel medicine developed as a completely new standard of care for first-line stem cell mobilization for all patients and donors," said John DiPersio, M.D., Ph.D., Professor of Medicine and Chief of the Oncology Division, Washington University School of Medicine, St. Louis, Missouri. "The data presented at TCT show safe and robust mobilization of sufficient cells for transplant in hours with MGTA-145 and plerixafor, compared to the typical five or more days of dosing required for G-CSF. Additionally, we saw rapid engraftment of the cells collected in the Phase 1 study in humanized mouse models."

Magenta has completed dosing in this Phase 1 trial, achieving all primary and secondary endpoints. The Company plans to move the MGTA-145 program into multiple Phase 2 studies in 2020. The Phase 2 studies will include both allogeneic and autologous transplant settings across multiple diseases and will evaluate mobilization and collection of high-quality cells and engraftment of the cells after transplant.

MGTA-145 Phase 1 Trial in Healthy Volunteers

These data provide further confirmation that MGTA-145, in combination with plerixafor, enables the same-day dosing and collection of sufficient hematopoietic stem cells (HSCs) for transplant.

Title: Phase 1 Clinical Study of MGTA-145 in Combination with Plerixafor Shows Rapid Single-Day Mobilization and Collection of CD34+ HSCs without G-CSF (Abstract #73)

Presenter: John DiPersio, M.D., Ph.D., Professor of Medicine and Chief of the Oncology Division, Washington University School of Medicine, St. Louis, Missouri

This study consists of four parts:

Part A: Healthy volunteers were dosed with a single dose of MGTA-145 or placebo.
Part B: Subjects received a single dose of MGTA-145 or placebo, in combination with plerixafor.
Part C: Subjects received a single dose of MGTA-145 or placebo, in combination with plerixafor on two consecutive days.
Part D: Eight subjects received a single of dose of MGTA-145 (0.03 or 0.015 mg/kg) in combination with plerixafor, followed by a single apheresis collection of multiple blood volumes.
Endpoints include safety and tolerability, pharmacokinetics and pharmacodynamic effects.

MGTA-145 was safe and well-tolerated as a single agent and in combination with plerixafor and showed the expected target pharmacology.
MGTA-145 engages CXCR2 on neutrophils to mobilize CD34+ cells into peripheral blood with limited neutrophil activation, which may minimize risk of adverse events typically seen with current standard of care.
Ten of 12 subjects who received a single dose of the combination of MGTA-145 at the .03 dose level or .015 dose level and plerixafor mobilized more than 20 CD34+ cells/microliter, the clinically accepted threshold for successful mobilization, in a single day.
Subjects in Part C demonstrated reliable mobilization of CD34+ cells on Day 2 with peak counts that were comparable to Day 1 mobilization yields, suggesting that two-day dosing and collection is feasible.
Single-day dosing and apheresis collection in eight subjects across two dose ranges administered in Part D yielded a median of 4.1 million CD34+ cells/kg.
The clinically accepted threshold for a successful transplant is 2 million cells/kg.
The median percentage of CD34+CD90+ cells (functional stem cells) was 35%, compared to approximately 10% with standard of care.
Stem cells collected from the first two subjects dosed in Part D transplanted into humanized mice engrafted more rapidly and at a 10-fold higher level than G-CSF-mobilized peripheral blood at a 12-week timepoint.
MGTA-145 in combination with plerixafor enables safe, same-day dosing, mobilization and collection of sufficient functional hematopoietic stem cells for transplant.