On December 1, 2018 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported late interim results from its BP-004 European registration trial, suggesting that adding rivo-celTM (rivogenlecleucel, formerly BPX-501) to stem cell transplants in patients who lack a matched donor may deliver comparable outcomes to matched unrelated donor (MUD) transplants (Press release, Bellicum Pharmaceuticals, DEC 1, 2018, View Source [SID1234531767]). The data were reviewed in a presentation today at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (ASH 2018) by Mattia Algeri, M.D., Cell and Gene Therapy Unit, Ospedale Bambino Gesù, Rome, Lazio, Italy.

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The interim data show a 90.9 percent event-free survival (EFS) rate at 180 days for patients treated with rivo-cel (n=166) after a stem cell transplant from a haploidentical, or partially matched, donor. These results appear comparable to an interim evaluation of patients who received a MUD transplant in the concurrently-run observational study (n=91), demonstrating an 87.7 percent EFS rate at 180 days. The Company expects to report final comparison results from both study populations and file for approval in Europe in 2019. Demonstrating non-inferiority to MUD transplantation is the primary study objective required for rivo-cel product registration in Europe.

"While a stem cell transplant is an established, often curative treatment option for children with cancers and hereditary blood diseases, the majority of patients are unable to find an HLA-matched related donor, which is associated with the best outcomes," commented Dr. Algeri. "While matched unrelated donor transplants are an important option, only half of patients can identify a match. Further, it can take up to several months to do so, a delay that is problematic for many transplant patients. These data suggest that rivo-cel treatment may enable haploidentical stem cell transplant with overall outcomes similar to MUD, making it an attractive alternative for many of these patients."

Study Design and Highlights

The BP-004 trial is a prospective, multicenter, European Phase 1/2 trial in pediatric patients with malignant or nonmalignant disorders. Patients received rivo-cel within a few weeks following a haplo-transplant. No post-transplant Graft versus Host Disease (GvHD) prophylaxis was used. Patients who developed visceral GvHD or were refractory to standard of care treatments were eligible to receive rimiducid. The primary endpoint was EFS at day 180 (events included transplant-related mortality or non-relapse mortality for malignant patients, severe GvHD, and life-threatening infections).

Rivo-cel was well-tolerated, with few patients experiencing non-GvHD adverse events considered to be possibly or probably related to rivo-cel. Overall GvHD rates were low, with few cases of high-grade acute GvHD or chronic GvHD. The majority of patients with visceral GvHD or who were refractory to standard of care treatment for GvHD responded to rimiducid.

The observational comparator trial (C/CP-004) was designed to collect both prospective and retrospective data from pediatric patients with either malignant or nonmalignant disease who underwent a matched unrelated donor transplant during the same time period and at the same treatment centers where the BP-004 rivo-cel study was conducted.

"These interim data increase our confidence that rivo-cel may be an approvable new treatment option for transplant patients with leukemias, lymphomas and genetic blood diseases in Europe upon final data read-out in 2019," commented Rick Fair, Bellicum President & CEO. "If we continue to demonstrate that rivo-cel enables patients without a matched donor to achieve outcomes comparable to a MUD transplant, that would be very clinically meaningful and would fulfill a requirement for European approval. We look forward to reporting final six-month results for all patients in 2019. We also plan to continue to follow these patients to evaluate the impact of rivo-cel in preventing relapse and extending overall survival, particularly in patients with leukemia."

A copy of this ASH (Free ASH Whitepaper) presentation will be made available in the Abstracts & Presentations section of the Company’s website. The Company expects to report topline final results in early 2019 followed by publication of a comprehensive data set.

Analyst and Investor Luncheon Event and Webcast
Bellicum will host a live and webcast analyst and investor luncheon event on December 3, 2018 at 12:00 p.m. – 1:30 p.m. PST in San Diego, CA. Featured speakers include Dr. Alice Bertaina, Associate Professor of Pediatrics (Stem Cell Transplantation), Lucile Packard Children’s Hospital at the Stanford School of Medicine, as well as Bellicum senior management. A webcast replay of the event will be available in the News & Events section of the Bellicum website, and available for at least two weeks following the event.

About Rivo-cel (BPX-501)
Rivo-celTM (rivogenlecleucel) is an allogeneic polyclonal T cell product designed to reduce relapse of leukemia following a stem cell transplant. The cell treatment contains a diverse repertoire of T cells which may contribute to a robust graft vs. leukemia effect. Rivo-cel’s antiviral benefits may also reduce morbidity and mortality in patients susceptible to infection following a transplant. The product’s CaspaCIDe safety switch enables this approach by allowing physicians to reduce the number of alloreactive cells in the event of uncontrolled GvHD. Rivo-cel addresses a major unmet need in adult and pediatric leukemia, lymphoma and genetic blood disease patients following a haploidentical stem cell transplant.

On December 1, 2018 Oncopeptides AB (Nasdaq Stockholm: ONCO) reported a presentation of the first interim data with melflufen (Ygalo) from the ongoing phase I/II study ANCHOR at the 60th ASH (Free ASH Whitepaper) meeting in San Diego, California, USA (Press release, Oncopeptides, DEC 1, 2018, View Source [SID1234531802]).

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Overall conclusions

The combinations of melflufen and dexamethasone (dex) with either bortezomib or daratumumab in relapsed-refractory multiple myeloma (RRMM) patients are well tolerated
No dose limiting toxicity has been observed at the melflufen 30 and 40 mg dose levels in either regimens. The 40 mg dose level is still recruiting patients
An Overall Response Rate (ORR) of 86% was observed with melflufen and dexamethasone in combination with daratumumab (CD38-directed monoclonal antibody)
An Overall Response Rate (ORR) of 100% was observed with melflufen and dexamethasone in combination with bortezomib (proteasome inhibitor)
The data are presented in a poster that can be found at: www.oncopeptides.com / presentations / 60th ASH (Free ASH Whitepaper)

CEO comments

"Although, these are early data and small patient samples, it is encouraging to see that melflufen is well tolerated and has a very high level of activity with no cross resistant pattern in combination regimens. These patients have undergone 2-3 prior lines of therapy and have developed resistant disease. The interim data show a very good efficacy profile for melflufen in combination with either bortezomib or daratumumab. In a cross-study comparison in RRMM patients treated with combination regimens our interim data with an ORR in the range 86-100% stand out positively. The treatment landscape changes over time and there is a high need of new treatment options with a novel mechanism of action like melflufen" said Jakob Lindberg, CEO of Oncopeptides.

About the ANCHOR study

The study recruitment is ongoing. ANCHOR is a phase I/II study where melflufen and dexamethasone (dex) is dosed in combination with either bortezomib or daratumumab. All patients must have 1-4 prior lines of therapy and be refractory (or intolerant) to an immunomodulary agent (IMiD) or a proteasome inhibitor (PI) or both.

In combination with bortezomib (Regimen A) patients cannot be refractory to a PI and in combination with daratumumab (Regimen B) patients cannot be previously exposed to any anti-CD38. Patients will be treated until documented disease progression or unacceptable toxicity. The primary objective of the phase I part of the study is to determine the optimal dose of melflufen and dex, up to a maximum of 40 mg, in combination with bortezomib or daratumumab. An additional 20 patients per regimen will be recruited in the phase II part of the study where the primary objective is ORR.

Summary of the ANCHOR interim data

Melflufen in combination with bortezomib – Regimen A

At the time of the data cut-off November 12, 2018, 3 patients had been treated with 30 mg melflufen and dex in combination with bortezomib. Median age was 81 years with a median of 3 prior lines of therapy. All patients were relapsed-refractory and 2 out of 3 patients were last line refractory (disease progression while on therapy). All patients were ongoing at the time of the data cut-off with a median treatment duration of 5.8 months.

The patients received a total of 17 cycles of treatment with a median of 7. All 3 patients achieved partial response (PR). No dose limiting toxicities were observed at the 30 mg melflufen dose level and the melflufen 40 mg has been opened for enrollment. The regimen was well tolerated with clinically manageable G3/4 hematological AEs and the low number of non-hematological AEs was noteworthy.

Melflufen in combination with daratumumab – Regimen B

At the time of the data cut-off, November 12, 2018, 9 patients had been treated with melflufen in combination with daratumumab and dex. Median age was 63 years with a median of 2 prior lines of therapy. No patient had achieved CR in any previous line of therapy, 67% were IMiD refractory and 56% were last line refractory (disease progression while on therapy). All patients were ongoing at the time of the data cut-off.

All 9 patients were still ongoing with a median treatment duration of 3.9 months. They received a total of 39 cycles of treatment with a median of 4.

Overall response rate N/A*
ORR CR VGPR PR MR SD PD
total, N=9 86% 0 4 2 0 1 0 2
*2 of the 9 patients were still in their first cycle of treatment and were therefore not evaluable for response as described at time for data cut.

4 patients were treated with 30 mg melflufen and 5 patients were treated with 40 mg melflufen with no dose limiting toxicity observed. The combination of melflufen, dexamethasone and daratumumab was well tolerated with clinically manageable G3/4 hematological AEs and the low number of non-hematological AEs was noteworthy.

About Melflufen

Melflufen (Ygalo), a peptide conjugated alkylator belonging to a novel class of peptidase-enhanced compounds, targets multiple myeloma (MM) cells with a unique mechanism of action. Aminopeptidases are enzymes found in all cells but are over-expressed in several cancers including MM. Ygalo selectively targets MM cells through aminopeptidase-driven accumulation. In vitro experiments show a 50-fold enrichment of the active substance in MM cells compared with administration of equal amount of an alkylator not enriched by aminopeptidases. The enrichment results in selective cytotoxicity (increased on-target potency and decreased off-target toxicity), and that resistance pathways of existing myeloma treatments (including alkylators) is overcome. Melflufen also demonstrates strong anti-angiogenic properties.

Melflufen in clinical development

Melflufen (Ygalo) has been used to treat late-stage RRMM patients in both phase I and phase II clinical studies (O-12-M1) with favorable results. Currently, melflufen is being studied in four clinical trials for the treatment of multiple myeloma. The current studies are OCEAN, HORIZON, ANCHOR and BRIDGE.

The current clinical study program is intended to demonstrate better results from treatment with melflufen compared to established alternative drugs for patients with multiple myeloma. Melflufen could potentially provide physicians with a new treatment option for patients suffering from this serious disease.

Melflufen has been investigated in the treatment of late-stage relapsed refractory multiple myeloma (RRMM) patients. This was done in the clinical study O-12-M1 where strong final results were reported in December 2017. Currently, four clinical studies are ongoing with melflufen.

OCEAN is Oncopeptides pivotal Phase III study where melflufen is compared directly with current standard of care, pomalidomide, in late-stage RRMM patients.

HORIZON is a Phase II study that studies the effect of melflufen in late-stage RRMM patients with few or no remaining established treatment options. Updated interim data from this study will be presented at ASH (Free ASH Whitepaper) in December 2018.

ANCHOR is a phase I/II study where melflufen is administered in combination with either bortezomib or daratumumab in RRMM patients. The results of this study aim to create understanding and knowledge among treating physicians for how melflufen can be used in combination with these drugs. In addition, the results could open up for the use of melflufen in earlier lines of treatment.

BRIDGE is a phase II study, where melflufen is used in RRMM patients with impaired renal function. This is a positioning study to show melflufen’s treatment profile in these patients.

On December 1, 2018 ArQule, Inc. (Nasdaq:ARQL) reported that it will present clinical data on the company’s BTK inhibitor, ARQ 531, in a poster presentation at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition to be held from December 1 to 4, 2018 in San Diego (Press release, ArQule, DEC 1, 2018, View Source [SID1234531787]).

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Updated safety, PK, biomarker and anti-tumor activity data from the company’s Phase 1 dose escalation study in patients with relapsed or refractory hematologic malignancies (ARQ 531-101) will be presented.

Presentation Details

Title:

A Phase 1 Dose Escalation Study of ARQ 531 in Selected Patients with Relapsed or Refractory Hematologic Malignancies

Abstract #: 3136
Session: CLL: Therapy, excluding Transplantation: Poster II
Date: Sunday, December 2, 2018
Time: 6:00-8:00 p.m. PT
Location: San Diego Convention Center, Hall GH

About BTK and ARQ 531
Bruton’s tyrosine kinase, BTK, is a therapeutic target that has been clinically proven to inhibit B-cell receptor signaling in blood cancers. ARQ 531 is an orally bioavailable, potent and reversible BTK inhibitor. Biochemical and cellular studies have shown that ARQ 531 inhibits both the wild type and C481S-mutant forms of BTK. The C481S-mutation is a known resistance mechanism for first generation irreversible BTK inhibitors. In preclinical studies, ARQ 531 has demonstrated good oral bioavailability as well as favorable pharmacokinetic, pharmacodynamic and metabolic properties.

On December 1, 2018 X4 Pharmaceuticals, a clinical stage biotechnology company developing novel CXCR4 allosteric antagonist drugs to improve immune cell trafficking to treat rare diseases and cancer, reported the presentation of additional Phase 2 clinical data demonstrating a positive safety profile and clinical activity of X4P-001 in patients with WHIM syndrome, a rare primary immunodeficiency disease (Press release, X4 Pharmaceuticals, DEC 1, 2018, View Source [SID1234531788]). The clinical results are being presented today in a poster session at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place in San Diego.

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"We continue to see encouraging results from this Phase 2 trial, as X4P-001 drug exposure appears to correlate with increases in absolute neutrophil count and absolute lymphocyte count levels. Increases in these biomarkers are an indication of potential improvement in the pathophysiology underlying WHIM syndrome. An example of clinical improvement and impact on symptoms was the continued reduction in a WHIM patient’s human papillomavirus-related warts following X4P-001 therapy," said David C. Dale, MD, Professor of Medicine at the University of Washington School of Medicine, Seattle, WA, and lead investigator of the trial.

The poster presentation at ASH (Free ASH Whitepaper) describes results from the first 8 patients with genetically confirmed WHIM syndrome and demonstrates the dose-dependent biomarker activity used to support dose selection for the Phase 3 trial. Additional updates on safety and clinical activity across all patients who were enrolled as of the August 17, 2018 data-cut off are also presented in the poster.

Information about the clinical trial of X4P-001 in patients with WHIM syndrome can be found on clinicaltrials.gov: View Source

"X4P-001 in WHIM syndrome is X4’s lead product candidate and our team is rapidly advancing toward the Phase 3 trial, with the goal of delivering X4P-001 to the global community of WHIM patients who currently lack any approved treatment specifically for this disease," said Paula Ragan, PhD, president and chief executive officer of X4 Pharmaceuticals. "We are confident in our path forward based on these favorable Phase 2 results, and we look forward to starting the pivotal Phase 3 trial in the first half of 2019."

About WHIM Syndrome
WHIM syndrome is a primary immunodeficiency disease caused by genetic mutations in the CXCR4 receptor gene resulting in susceptibility to certain types of infections. WHIM is an abbreviation for the characteristic clinical symptoms of the syndrome: Warts, Hypogammaglobulinemia, Infections, and Myelokathexis. Within the overall category of primary immunodeficiencies, there are between 15,000 and 100,000 patients in the U.S. who are classified with primary immunodeficiency disease of unknown origin – of which WHIM is one.1,2,3 WHIM syndrome is a rare disorder and the precise prevalence or incidence of patients that have the genetic mutation responsible for WHIM syndrome is unknown. Individuals with WHIM syndrome are more susceptible to potentially life-threatening bacterial infections.4 Additionally, WHIM syndrome is associated with significant morbidity beginning in early childhood and continuing throughout life. Current therapy is limited to treatment of acute infections with antibiotics or prevention of infections through the use of intravenous immunoglobulin or G-CSF. There is no approved therapy for the treatment of WHIM syndrome.

On December 1, 2018 Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of bone marrow transplant to more patients, reported that the Company highlighted new preclinical research on its MGTA-145 product candidate for stem cell mobilization in an oral presentation at the 60th annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, Magenta Therapeutics, DEC 1, 2018, View Source [SID1234531773]). MGTA-145 is being developed as a first-line agent to enable single-day mobilization of high numbers of hematopoietic stem cells for bone marrow transplant.

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"Seventy percent of the bone marrow transplants performed in the US and Europe each year use mobilized peripheral blood as a source of stem cells, but current standards of care require four to six days to mobilize an adequate number of stem cells. This is a notable burden on patients, donors and healthcare resources, and the standard treatment may be contraindicated or not tolerated in some patients who need transplant," said John Davis, M.D., M.P.H, chief medical officer, Magenta Therapeutics. "Data at ASH (Free ASH Whitepaper) this year show that MGTA-145, used in combination with plerixafor, rapidly mobilizes robust numbers of stem cells that successfully engrafted in non-human primates, and the cells mobilized by the combination also blocked GvHD in a preclinical model. Based on the body of preclinical data we have seen with MGTA-145, we will be moving this program into the clinic in the first half of 2019 as a promising investigational first-line therapy for stem cell mobilization."

MGTA-145 in Combination with Plerixafor Rapidly Mobilizes High Numbers of Hematopoietic Stem Cells and Graft-Versus-Host Disease-Inhibiting Myeloid-Derived Suppressor Cells in Non-Human Primates, Abstract #116

Key results, presented by Patrick Falahee, Ph.D., Magenta Therapeutics:

MGTA-145 works synergistically with plerixafor, another agent for stem cell mobilization, to rapidly mobilize large numbers of stem cells.
A single injection of MGTA-145 plus plerixafor mobilized sufficient stem cells for transplant within five hours in non-human primates.
A single injection of MGTA-145 plus plerixafor mobilized 2 to 3 times the number of stem cells in four hours compared to the number mobilized over five days with standard of care agent G-CSF in non-human primates.
When the cells mobilized with MGTA-145 plus plerixafor were transplanted into a non-human primate model, they rapidly engrafted.
MGTA-145 plus plerixafor led to a 3-fold increase in immunosuppressive monocytes mobilized over G-CSF – and the mobilized cells blocked GvHD, a significant challenge in allogeneic bone marrow transplant.