On September 16, 2019 Blue Earth Diagnostics, a Bracco company focused on molecular imaging diagnostics, reported results from an investigational clinical trial ("FALCON") evaluating the impact of 18F-fluciclovine PET/CT imaging on the clinical management of men with biochemically recurrent prostate cancer eligible for salvage therapy (Press release, Blue Earth Diagnostics, SEP 16, 2019, View Source [SID1234539543]). The FALCON trial is a UK-based, prospective, multi-center, open-label study (NCT02578940). Its primary endpoint examined the percentage of men who had their management plan changed after an 18F-fluciclovine PET/CT scan.

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Axumin (fluciclovine F 18) injection is approved for use in positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood levels of prostate specific antigen (PSA) following prior treatment. (For additional product information please see the end of this news release.)

Investigators in the FALCON trial recorded intended patient management plans prior to 18F-fluciclovine PET/CT imaging and then recorded how the plans were altered following review of the scan results. Results of the trial indicated that 64% (66/104) of patients had their clinical management plan changed when results of 18F-fluciclovine PET/CT imaging were added to the standard-of-care diagnostic work-up. Of those changes, 65% (43/66) were classified as "major," denoting a change in treatment modality (e.g. salvage radiotherapy to androgen deprivation therapy (ADT)).

Results from the study were summarized in an oral presentation, "Impact of positron emission tomography (PET) with 18F-fluciclovine PET/CT on management of patients with recurrence of prostate cancer: results from the FALCON trial," by David Bottomley, MBBS, St. James Institute of Oncology, Leeds UK, at the 2019 American Society for Radiology Oncology (ASTRO) Annual Meeting, September 15 – 18, 2019.

"We are very pleased to share results from the FALCON study with the radiation oncology community at ASTRO and look forward to publishing the results in an upcoming peer-reviewed journal," said Jonathan Allis, D. Phil., CEO of Blue Earth Diagnostics. "As part of our mission to develop and commercialize innovative PET imaging agents for cancer, Blue Earth Diagnostics conducted the FALCON and LOCATE studies to evaluate the utility of a 18F-fluciclovine PET/CT scan in providing physicians with actionable information for the management of men with recurrent prostate cancer. Each of these two independent, prospective studies arrived at similar conclusions – that 18F-fluciclovine PET/CT located recurrent disease in the majority of men in the study, which frequently resulted in major changes to their management plans for biochemical recurrence."

"The FALCON study evaluated men with biochemically recurrent prostate cancer who were being considered for curative-intent salvage therapy, and compared their treatment plans before and after 18F-fluciclovine PET/CT imaging to assess whether or not it impacted their management," said David Bottomley, MD, St. James Institute of Oncology, Leeds UK. "Results indicated that management plans were revised for the majority of patients, with 65% of revisions involving a major change in treatment modality. These results indicate that decisions based on 18F-fluciclovine PET/CT findings may facilitate more personalized management in men with biochemically recurrent prostate cancer. Investigation of the long-term clinical outcomes of these changes in management is warranted."

The primary endpoint of the FALCON trial examined the percentage of men who had their management plan changed following an 18F-fluciclovine scan. Previously planned therapeutic management was revised after an 18F-fluciclovine PET/CT scan in 64% (66/104) of patients. Of the patients with revised treatment plans, major revisions (e.g., salvage radiotherapy to hormone deprivation or watchful waiting) were made for 65% (43/66) of patients. Salvage treatment was revised to watchful waiting for 24% (16/66) patients and to systemic therapy for 24% (16/66) patients, and 17% (11/66) experienced alternative changes to their treatment modality. Of the patients with revised treatment plans, 35% (23/66) had their intended radiotherapy/brachytherapy plans modified. The safety profile of 18F-fluciclovine in the FALCON trial is consistent with that described in the approved U.S. Prescribing Information.

"Between 30 – 40% of patients with prostate cancer will develop local or distant recurrences within 10 years of radical prostatectomy or radiation therapy, underscoring the need for accurate information on the extent and location of recurrent disease," said Gerald L. Andriole, MD, the Robert K. Royce Distinguished Professor and Chief of Urologic Surgery at Washington University School of Medicine and lead author on behalf of the LOCATE study group. "Results of the FALCON study are consistent with those of the U.S., multi-center LOCATE study of 213 patients, which demonstrated that 59% of men with recurrent prostate cancer following prior treatment had a change in their management plan after 18F-fluciclovine PET/CT imaging."

About the FALCON Trial

The FALCON trial, "Fluciclovine (18F) PET/CT in biochemicAL reCurrence Of prostate caNcer (FALCON)," was an open-label, multi-center study in the UK designed to assess the clinical utility of 18F-fluciclovine PET imaging in the management of patients with prostate cancer with biochemical recurrence after initial treatment. The primary endpoint was to evaluate the clinical impact of 18F-fluciclovine in affecting treatment decisions and was assessed by comparing records of the patient’s treatment plan after an 18F-fluciclovine PET scan with the treatment plan prior to the scan. Secondary endpoints included evaluation of the optimal PSA threshold for detection, salvage treatment outcome assessment based on 18F-fluciclovine involvement and safety.

The FALCON trial was jointly funded by Innovate UK and Blue Earth Diagnostics and was conducted at six leading institutions in the UK: Oxford University Hospitals NHS Foundation Trust, University College London, Kings College London, The Royal Marsden NHS Foundation Trust, The Leeds Teaching Hospitals NHS Trust, Mount Vernon Cancer Centre and Greater Glasgow Health Board. Additional information about the FALCON trial is available at: www.clinicaltrials.gov (NCT02578940).

This press release is intended to provide information about Blue Earth Diagnostics’ business in the United States and Europe. Please be aware that the approval status and product label for Axumin varies by country worldwide. For EU Axumin product information refer to: View Source;mid=WC0b01ac058001d124.

U.S. INDICATION AND IMPORTANT SAFETY INFORMATION ABOUT AXUMIN
INDICATION
Axumin (fluciclovine F 18) injection is indicated for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment.

IMPORTANT SAFETY INFORMATION

Image interpretation errors can occur with Axumin PET imaging. A negative image does not rule out recurrent prostate cancer and a positive image does not confirm its presence. The performance of Axumin seems to be affected by PSA levels. Axumin uptake may occur with other cancers and benign prostatic hypertrophy in primary prostate cancer. Clinical correlation, which may include histopathological evaluation, is recommended.
Hypersensitivity reactions, including anaphylaxis, may occur in patients who receive Axumin. Emergency resuscitation equipment and personnel should be immediately available.
Axumin use contributes to a patient’s overall long-term cumulative radiation exposure, which is associated with an increased risk of cancer. Safe handling practices should be used to minimize radiation exposure to the patient and health care providers.
Adverse reactions were reported in ≤ 1% of subjects during clinical studies with Axumin. The most common adverse reactions were injection site pain, injection site erythema and dysgeusia.
To report suspected adverse reactions to Axumin, call 1-855-AXUMIN1 (1-855-298-6461) or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Full Axumin prescribing information is available at www.axumin.com.

About Axumin (fluciclovine F 18)

Axumin (fluciclovine F 18) injection is a novel product indicated for use in positron emission tomography (PET) imaging to identify suspected sites of prostate cancer recurrence in men. Recurrence of prostate cancer is suspected by an increase in prostate specific antigen (PSA) levels following prior treatment. PET imaging with Axumin may identify the location and extent of such recurrence. Axumin was developed to enable visualization of the increased amino acid transport that occurs in many cancers, including prostate cancer. It consists of a synthetic amino acid that is preferentially taken up by prostate cancer cells compared with surrounding normal tissues and is labeled with the radioisotope F 18 for PET imaging. Fluciclovine F 18 was invented at Emory University in Atlanta, Ga., with much of the fundamental clinical development work carried out by physicians at Emory University’s Department of Radiology and Imaging Sciences. Axumin was approved by the U.S. Food and Drug Administration in May 2016, following Priority Review, and is the first product commercialized by Blue Earth Diagnostics, which licensed the product from GE Healthcare. The molecule is being investigated by Blue Earth Diagnostics for other potential cancer indications including neuro-oncology.

On September 16, 2019 Precision BioSciences, Inc. (Nasdaq: DTIL), a genome editing company dedicated to improving life through the application of its pioneering, proprietary ARCUS platform, reported the U.S. Food and Drug Administration (FDA) has accepted its Investigational New Drug (IND) application for PBCAR20A, the Company’s second off-the-shelf chimeric antigen receptor (CAR) T cell therapy program (Press release, Precision Biosciences, SEP 16, 2019, View Source [SID1234539541]). Wholly owned by Precision, PBCAR20A is an allogeneic anti-CD20 CAR T therapy candidate in development for the treatment of non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL). The company plans to initiate a Phase 1/2a clinical trial in the fourth quarter of 2019, with initial data expected in 2020. The study will include patients with NHL, of which a subset will have the diagnosis of mantle cell lymphoma (MCL). Precision BioSciences has received Orphan Drug Designation for MCL and plans to pursue this indication.

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"FDA clearance to begin clinical trials with our anti-CD20 off-the-shelf CAR T therapy candidate is a significant milestone for Precision. Closely following the initiation earlier this year of our first clinical trial with the anti-CD19 allogeneic CAR T therapy candidate PBCAR0191, today’s announcement demonstrates our ability to advance multiple product candidates in parallel into the clinic, leveraging the unique capabilities of our ARCUS genome editing platform, CAR T development approach and a highly differentiated manufacturing process developed in house," commented Matt Kane, Chief Executive Officer and Co-Founder of Precision BioSciences. "I am delighted that our team continues to deliver ahead of expectations."

David Thomson, Chief Development Officer of Precision, said, "In preclinical disease models, PBCAR20A has demonstrated potent in vivo clearance of CD20+ tumor cells and overall tumor volume reduction. Furthermore, we did not observe any evidence of graft-versus-host disease in strict preclinical models. It is our hope that PBCAR20A will provide a new allogeneic CAR T therapy option with the benefits of reliable, off-the-shelf access and optimized cellular activity to patients living with NHL or CLL/SLL, where a significant need for new treatment options remains. Receiving orphan drug designation from the FDA for MCL means that we have a special opportunity to serve those patients previously treated for the MCL form of NHL, who have a poor prognosis with currently available treatments."

PBCAR20A will be Precision’s second off-the-shelf CAR T therapy candidate to enter the clinic, following PBCAR0191, an off-the-shelf anti-CD19 CAR T therapy candidate currently being evaluated in adult patients with relapsed or refractory (R/R) NHL or R/R B-cell precursor acute lymphoblastic leukemia (B-ALL). Precision initiated dosing of subjects in a Phase 1/2a clinical trial of PBCAR0191 in April 2019, which continues to progress as planned; the company expects to present interim data from this trial at a scientific conference no later than the first quarter of 2020.

With the IND acceptance and expected upcoming clinical trial initiation for PBCAR20A, Precision’s clinical-stage portfolio of off-the-shelf CAR T therapy candidates for B-cell malignancies continues to grow. In the United States, B-cell malignancies account for 85 percent of all NHL cases, and CLL and SLL represent 25 to 30 percent of leukemias. While front-line treatments provide benefit to more than half of newly diagnosed NHL patients, at least a third of those who do benefit will become refractory, achieve only partial remission or relapse after remission. In addition, patients with CLL have seen limited success with autologous CAR T cell therapies, which is commonly ascribed to T cell exhaustion associated with this malignancy. Administration of healthy donor T cells via allogeneic CAR T cell therapy has the potential to overcome current challenges in CLL treatment, increase access to care in NHL and overcome treatment resistance due to CD19 loss. In addition, allogeneic CAR T therapy presents the possibility for combination treatment options by targeting both CD19 and CD20, which may help overcome resistance mechanisms in some patients.

Precision’s Off-The-Shelf CAR T Platform
Precision is advancing a pipeline of cell-phenotype optimized allogeneic CAR T therapies, leveraging fully scaled, proprietary manufacturing processes. The platform is designed to maximize the number of patients who can potentially benefit from CAR T therapy. Precision carefully selects high-quality T cells derived from healthy donors as starting material, then utilizes its unique ARCUS genome editing technology to modify the cells via a single-step engineering process. By inserting the CAR gene at the T cell receptor (TCR) locus, this process knocks in the CAR while knocking out the TCR, creating a consistent product that can be reliably and rapidly manufactured and is designed to prevent graft-versus-host disease. Precision optimizes its CAR T therapy candidates for immune cell expansion in the body by maintaining a high proportion of naïve and central memory CAR T cells throughout the manufacturing process and in the final product.

About the PBCAR20A Clinical Trial
PBCAR20A will be evaluated in a Phase 1/2a multicenter, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation and dose-expansion clinical trial in adult NHL, CLL, and SLL patients. The trial will be conducted at multiple U.S. sites. For more information on the trial, visit www.clinicaltrials.gov, study identifier number NCT04030195.

On September 16, 2019 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), an oncology-focused pharmaceutical company, reported its entry into a royalty agreement with HealthCare Royalty Partners (HCR) for up to $150 million to support the ongoing development and commercialization of XPOVIOTM (selinexor), the Company’s first-in-class, oral SINE compound, which is currently marketed in the U.S. for the treatment of patients with heavily pretreated multiple myeloma (Press release, Karyopharm, SEP 16, 2019, View Source [SID1234539509]). Selinexor is also in late-stage clinical development for the treatment of patients with relapsed or refractory multiple myeloma who have had one to three prior lines of therapy and for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

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Under the terms of the agreement, Karyopharm will receive $75 million at closing this month and is eligible to receive an additional $75 million upon the achievement of future regulatory and commercial milestones and subject to approval by both parties. In exchange for the amount received at the initial closing, HCR will receive a tiered royalty in the mid-single digits based on worldwide net revenues of XPOVIO and any other future products. Karyopharm expects that the $75 million initially received from HCR under this royalty agreement, combined with its existing cash, cash equivalents and investments, together with the cash expected to be generated from product sales, will be sufficient to fund its operations into the middle of 2021.

"This non-dilutive financing provides Karyopharm with immediate and substantial capital to support the ongoing commercialization of XPOVIO in patients with heavily pretreated multiple myeloma, and further the development of selinexor in future high unmet need indications," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "We are delighted to have the support and confidence of HealthCare Royalty Partners, a premier partner known for its strategic investments in promising healthcare companies and assets."

Clarke Futch, Managing Partner and Chairman of the Investment Committee of HealthCare Royalty Partners stated: "Based on our extensive due diligence, we believe XPOVIO’s strong commercial prospects and upside potential creates an attractive investment profile for HCR. The Karyopharm leadership team has deep expertise in bringing innovative drugs to market for the treatment of high unmet need cancers, and we are pleased to be partnering with them during this transformative time in the Company’s evolution."

XPOVIO received accelerated approval from the U.S. Food and Drug Administration (FDA) on July 3, 2019 for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. A Marketing Authorization Application (MAA) seeking conditional approval for selinexor is currently under review by the European Medicines Agency and Karyopharm expects to receive a decision on the MAA by early 2020.

Morgan Stanley & Co. LLC acted as sole structuring agent, and Goodwin Procter LLP acted as special transaction counsel, to Karyopharm on the transaction.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. In addition to receiving accelerated FDA approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody, Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor. Selinexor is also being studied in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). In 2018, Karyopharm reported positive top-line results from the Phase 2b SADAL study evaluating selinexor in patients with relapsed or refractory DLBCL after at least two prior multi-agent therapies and who are ineligible for transplantation, including high dose chemotherapy with stem cell rescue. Selinexor has received Fast Track designation from the FDA for the patient population evaluated in the SADAL study. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON), as a potential backbone therapy in combination with approved therapies (STOMP), in liposarcoma (SEAL), in recurrent gliomas (KING) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

On September 16, 2019 AstraZeneca reported that it will unveil a series of breakthrough data across multiple cancer types in its mission to one day eliminate cancer as a cause of death at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Barcelona, Spain, 27 September to 1 October 2019 (Press release, AstraZeneca, SEP 16, 2019, View Source [SID1234539503]).

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With 63 abstracts, including 7 oral presentations, the Company will demonstrate its leadership in precision medicine and immunotherapy. Highlights include results of three Phase III clinical trials featured in the ESMO (Free ESMO Whitepaper) Presidential Symposia across three cancer types:

In lung cancer, new data from the Phase III FLAURA trial will highlight the superior overall survival (OS) benefit of Tagrisso (osimertinib) compared with previous standard-of-care (SoC) treatments erlotinib or gefitinib for patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) (Abstract #LBA5_PR). FLAURA is the first and only global Phase III trial to demonstrate a statistically-significant OS benefit in this setting.
In ovarian cancer, progression-free survival (PFS) results from the Phase III PAOLA-1 trial, including key subgroup analysis, will illustrate the benefit of adding Lynparza (olaparib) to SoC bevacizumab in the 1st-line maintenance treatment of women with advanced ovarian cancer (Abstract #LBA2_PR). PAOLA-1 is the second positive Phase III trial for Lynparza in 1st-line advanced ovarian cancer.
In metastatic castration-resistant prostate cancer (mCRPC), results from the Phase III PROfound trial will detail the improvements in radiographic PFS observed with Lynparza. Patients in the trial had progressed on prior treatment with new hormonal anticancer treatments and had mutations in homologous recombination repair (HRR) genes, such as BRCA1/2 and ATM, which are a common trait in cancer cells that can interfere with normal cell DNA repair mechanisms (Abstract #LBA12_PR). These data show the value of genomic testing beyond just BRCAm and make Lynparza the first PARP inhibitor to achieve positive Phase III results in four different cancer types (breast, ovarian, pancreatic and prostate).
Dave Fredrickson, Executive Vice President, Oncology, said: "The practice-changing data we are presenting at ESMO (Free ESMO Whitepaper) 2019 demonstrates our commitment to make prolonged survival a realistic outcome. By using biomarkers to define optimal treatment and match innovative precision medicines to the patients who can best benefit from them, our dynamic Oncology pipeline and pioneering research continue to deliver new potential medicines across multiple deadly cancers."

José Baselga, Executive Vice President, Oncology R&D, said: "At ESMO (Free ESMO Whitepaper) 2019 we will see key components of our next-generation Oncology pipeline, including innovative platform studies and early data for the next wave of therapies designed to preferentially kill cancer cells and regulate the immune response to cancer."

Improving overall survival across lung cancers

In addition to the FLAURA OS results, key presentations include:

Results from the Phase III CASPIAN trial showing improved OS with better quality of life for patients taking Imfinzi (durvalumab) in combination with SoC chemotherapy vs. SoC (Abstract #LBA89).
New data from the Phase III PACIFIC trial demonstrating that treatment benefit with Imfinzi vs. placebo was maintained regardless of the occurrence of pneumonitis (Abstract #1459PD).
An oral presentation of data from the Phase I/II 1108 study in patients with solid tumours, including NSCLC, showing that reinitiating treatment with Imfinzi restored antitumour efficacy without disease progression in previously-treated patients who had progressed after a planned treatment interruption (Abstract #1175O).
Results from the real-world ASTRIS study of EGFR T790M mutation positive advanced NSCLC patients with central nervous system (CNS) metastases (Abstract #1521P).

Breaking treatment boundaries in ovarian cancer

In addition to the PAOLA-1 results, key presentations include:

Subanalyses from the Phase III SOLO-1 trial of Lynparza in newly-diagnosed advanced ovarian cancer patients, assessing time to second subsequent therapy (Abstract #995PD), patient-reported outcomes (Abstract #996PD) and health-related quality of life (HRQoL) (Abstract #998PD).
Updated results from the Phase II MEDIOLA trial of Lynparza and Imfinzi in germline BRCAm platinum-sensitive relapsed ovarian cancer (Abstract #1191PD).
Data from the Phase II BAROCCO trial of Lynparza and cediranib with a continuous or intermittent schedule in advanced platinum-resistant ovarian cancer (Abstract #LBA58).

Establishing new therapeutic landmarks in multiple tumour types

Presentations beyond the PROfound trial results include:

Subanalyses from the Phase III POLO trial of Lynparza in germline BRCAm metastatic pancreatic cancer patients, including HRQoL (Abstract #675PD) as well as time to treatment discontinuation and time to subsequent therapies (Abstract #693P).
An oral presentation of data from the Phase Ib BISCAY trial, an adaptive, biomarker-directed platform study of Imfinzi in combination with multiple targeted therapies in metastatic bladder cancer (Abstract #902O).
Preliminary results from the Phase I PATRIOT study of ATR inhibitor AZD6738 as monotherapy in advanced solid tumours (Abstract #450PD).
Safety data from a Phase I/II trial of Imfinzi plus monalizumab, bevacizumab and SoC combination chemotherapy in patients with metastatic microsatellite-stable colorectal cancer (Abstract #1201P).
Updated results from the MEDIOLA Phase II study of Lynparza and Imfinzi in germline BRCAm metastatic breast cancer (MBC) (Abstract #1191O).

On September 15, 2019 Oncopeptides AB (Nasdaq Stockholm: ONCO) reported updated interim efficacy and safety data from the ongoing pivotal Phase 2 study, HORIZON, at the 17th International Myeloma Workshop (IMW) meeting in Boston, Massachusetts, USA (Press release, Oncopeptides, SEP 15, 2019, View Source [SID1234539502]). The data focused on patients with extramedullary disease (EMD) and was presented in an oral presentation by Professor Paul G. Richardson. Oncopeptides will host a conference call to review this data on Monday, September 16, 2019, at. 08.30 (CET).

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The results presented at IMW 2019 by Professor Paul G Richardson in the plenary session "Late Breaking Abstracts" under the title: Activity of Melflufen in RRMM Patients with Extramedullary Disease in the Phase 2 Study (OP-106 HORIZON) – Promising Results in a High-Risk Population, are based on a data cut in the HORIZON study dated July 30, 2019 when 136 patients were treated compared to previously reported data including 121 patients. Based on literature, HORIZON represents the largest clinical cohort to date of myeloma patients with extra medullary disease (EMD).

Relapsed-refractory multiple myeloma (RRMM) patients with extramedullary disease (EMD) is a very difficult to treat patient population. In recent single-agent studies (with or without steroids) including RRMM patients with EMD have shown overall response rates (ORR) between 0 – 17%. Only daratumumab has shown any relevant clinical activity with a response rate of 17% in daratumumab naïve myeloma patients with EMD.

In the HORIZON study, an overall response rate of 23% was achieved with treatment with melflfufen and dexamethasone in RRMM patients with EMD. These patients were mainly penta refractory (had undergone at least five prior treatments and were resistant to at least one proteasome inhibitor, one IMiD, and anti-CD38 treatment). The EMD patients who responded to the treatment had a median survival (OS) of 18.5 months compared to a median survival of 5.1 months for the EMD patients who did not respond to treatment. The difference observed suggests a clear clinical benefit for these patients.

Professor Paul G Richardson comments
"We are experiencing a significant increase in the number of relapsed and refractory myeloma patients with extramedullary disease and without effective treatment options. The observation in the HORIZON trial, that melflufen shows activity in these patients and may impact favorably on survival outcome, is very encouraging.

"In my view, given the relative lack of therapeutic alternatives for these patients, moving rapidly into melflufen-based combination strategies in patients with extramedullary disease, as well as exploring earlier lines of therapy, should be the next priority", said Professor Paul G Richardson, Professor of Medicine at Harvard Medical School and Clinical Program Leader, Director of Clinical Research at the Jerome Lipper Multiple Myeloma Center Dana-Farber Cancer Institute in Boston, Massachusetts, USA.

Overall Conclusions From the Presentation

As of July 30, 2019, 136 patients had been treated in HORIZON with melflufen and dexamethasone. 44 out of the 136 patients had confirmed EMD diagnosis at baseline
91% of EMD patients were triple-class refractory and 73% penta refractory
Similar ORR in non-EMD and EMD patients with an ORR of 27% and 23% respectively
Response rates in EMD patients was seemingly higher than historical studies
Median OS was 5.8 months for patients with EMD and 11.6 months for patients without EMD
Median OS in EMD responders and non-responders was 18.5 months and 5.1 months, respectively
Median OS in non-EMD responders and non-responders was 17.2 months and 8.5 months, respectively
The treatment was generally well tolerated, with manageable toxicity with a low overall incidence of nonhematologic Adverse Events (AE) including infections; no treatment-related deaths
The full presentation from IMW is available on the company’s website under:
www.oncopeptides.com / Investors&media / Presentations / IMW 2019

Conference call for investors, analysts and the media
CEO Jakob Lindberg will review of the results presented at IMW, on Monday September 16, 2019 at 08:30 (CET).
The conference call will also be streamed via a link on the company website: www.oncopeptides.com.

Phone numbers for participants from:
Sweden: +46 8 505 583 68
Europe: +44 3333 009 271
USA: +1 833 823 05 87

The information in the press release is information that Oncopeptides is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person above, on September 15, 2019 at 14.30 (CET).

About the OP-106 HORIZON study
Patient recruitment in the HORIZON study is ongoing. The interim data presented at IMW 2019 is based on a data cut-off dated July 30, 2019, with 136 patients treated. The goal is to include 150 patients in the study. The patients in the study are refractory to pomalidomide and/or daratumumab after failing on immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs).

Oncopeptides has initiated preparations for submitting a New Drug Application (NDA) for accelerated approval of melflufen in the US based on the available HORIZON data. The detailed plan for the filing process is still under development, but Oncopeptides currently targets to submit the application to FDA during the first quarter of 2020. This could then lead to the first melflufen market approval in the US in 2020.

More information can be found at: View Source;rank=2

About Melflufen
Melflufen is a lipophilic peptide-conjugated alkylator that rapidly delivers a highly cytotoxic payload into myeloma cells through peptidase activity. It belongs to the novel class Peptidase Enhanced Cytotoxics (PEnC), which is a family of lipophilic peptides that exhibit increased activity via peptidase cleavage and have the potential to treat many cancers. Peptidases play a key role in protein homeostasis and feature in cellular processes such as cell-cycle progression and programmed cell death. Melflufen is rapidly taken up by myeloma cells due to its high lipophilicity and immediately cleaved by peptidases to deliver an entrapped hydrophilic alkylator payload. In vitro, melflufen is 50-fold more potent in myeloma cells than the alkylator payload itself due to the peptidase cleavage, and induces irreversible DNA damage and apoptosis. Melflufen displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, and has also demonstrated inhibition of DNA repair induction and angiogenesis in preclinical studies.