On May 13, 2020 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage oncology therapeutics company developing drugs to treat cancers with the greatest medical need for new treatment options, including KRAS-mutated colorectal cancer, Zytiga-resistant prostate cancer and leukemia, reported an agreement with PoC Capital, LLC, to fund the completion of its ongoing Phase 1b/2 clinical trial in patients with KRAS-mutated metastatic Colorectal Cancer (mCRC) (Press release, Trovagene, MAY 13, 2020, View Source [SID1234557893]).

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"We are pleased to be able to support the second phase of Cardiff Oncology’s clinical study of onvansertib in patients with KRAS-mutated colorectal cancer," said Daron Evans, Managing Director of PoC Capital. "The response in patients enrolled in the first phase of this study is very encouraging and we are optimistic that patients will soon have a new therapeutic option to treat their cancer."

Cardiff Oncology’s agreement with PoC Capital follows the Company’s announcement of positive safety and efficacy data from its Phase 1b trial, presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) conference. The data demonstrate clinical benefit in patients treated with onvansertib in combination with second line standard-of-care, FOLFIRI/Avastin. Seven out of eight (88%) evaluable patients achieved a clinical response (partial response + stable disease) and progression-free survival (PFS) of 6.5 months, which exceeds the current standard-of-care response rate of 4% and median PFS of 5.5 months. Additional trial data will be presented as a virtual oral poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting on Friday, May 29, 2020.

"Our agreement with PoC Capital is an important milestone and recognition of the efficacy we are already observing in our ongoing clinical trial targeting KRAS-mutated mCRC, an indication of high unmet medical need," said Dr. Mark Erlander, Chief Executive Officer of Cardiff Oncology. "We are pleased to continue our partnership with PoC Capital and advance our clinical development of onvansertib and address the once considered ‘undruggable’ KRAS mutation in an effort to improve response to treatment in patients who have previously been faced with a very poor prognosis."

Colorectal cancer (CRC) is the second leading cause of cancer death in the U.S. Despite significant progress in the treatment of mCRC, the majority of patients with metastatic disease succumb to the disease. Therefore, improving the treatment options and effectiveness is critical in changing the outcomes for this patient population. The efficacy of second-line therapy in terms of survival prolongation and response remains very limited, particularly in the KRAS-mutated population, where treatment options are more restricted. The response rate in the second-line setting is 4% and the median progression-free survival is 5.5 months as reported in a large international trial.
About the Phase 1b/2 Clinical Trial of Onvansertib in mCRC
In this open-label, Phase 1b/2 trial, onvansertib in combination with standard-of-care FOLFIRI and Avastin is being evaluated for safety and efficacy in patients with KRAS-mutated mCRC. The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second‑Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation, will enroll up to 44 patients with a KRAS mutation and histologically confirmed metastatic and unresectable disease. In addition, patients must have failed treatment or be intolerant of FOLFOX (fluoropyrimidine and oxaliplatin) with or without Avastin (bevacizumab). The trial is being conducted at two prestigious cancer centers: USC Norris Comprehensive Cancer Center and The Mayo Clinic Arizona.
About Onvansertib
Onvansertib is a first-in-class, third-generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK1) enzyme, which is over-expressed in multiple cancers including leukemias, lymphomas and solid tumors. Onvansertib targets the PLK1 isoform only (not PLK2 or PLK3), is orally administered and has a 24-hour half-life with only mild-to-moderate side effects reported. Cardiff Oncology believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.
Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including irinotecan, FLT3 and HDAC inhibitors, taxanes and cytotoxins. Cardiff Oncology believes the combination of onvansertib with other compounds has the potential to improve clinical efficacy in acute myeloid leukemia (AML), metastatic castration-resistant prostate cancer (mCRPC), non-Hodgkin lymphoma (NHL), colorectal cancer and triple-negative breast cancer (TNBC), as well as other types of cancer.
Cardiff Oncology has three ongoing clinical trials of onvansertib: A Phase 2 trial of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with mCRPC who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving Zytiga (NCT03414034); a Phase 1b/2 Study of onvansertib in combination with FOLFIRI and Avastin for second-line treatment in patients with mCRC with a KRAS mutation (NCT03829410; and a Phase 2 clinical trial of onvansertib in combination with decitabine in patients with relapsed or refractory AML (NCT03303339).
Cardiff Oncology licensed onvansertib (also known as NMS-1286937 and PCM-075) from Nerviano Medical Sciences (NMS), the largest oncology-focused research and development company in Italy, and a leader in protein kinase drug development. NMS has an excellent track record of licensing innovative drugs to pharma/biotech companies, including Array (recently acquired by Pfizer), Ignyta (acquired by Roche) and Genentech.

On May 13, 2020 Medica Therapeutics Inc. (Nasdaq: DMAC), a clinical-stage biopharmaceutical company focused on developing novel treatments for kidney diseases and neurological disorders, reported positive top-line results from ReMEDy, its Phase II study in acute ischemic stroke (AIS), as well as provided a business update and financial results for the three months ended March 31, 2020 (Press release, DiaMedica, MAY 13, 2020, View Source [SID1234557909]). DiaMedica will host a conference call with slides tomorrow, May 14, 2020, at 7:00 a.m. Central Time to discuss its ReMEDy top-line data, business update and first quarter financial results. In conjunction with this release, DiaMedica also issued today a separate more detailed release on the ReMEDy top-line data.

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Clinical Developments

DM199 for the Treatment of Acute Ischemic Stroke

DM199 Acute Ischemic Stroke Phase II "ReMEDy" Trial – Positive Top-Line Data

DiaMedica reported positive top-line results from its ReMEDy trial, a Phase II study assessing the safety, tolerability and therapeutic potential of DM199 in participants suffering from AIS. Final enrollment was 92 participants. The markers of therapeutic efficacy included the National Institutes of Health Stroke Scale, Modified Rankin Scale and the Barthel Index and multiple plasma-based biomarkers (e.g. C-reactive protein). These markers were assessed at multiple points throughout the study, including 90 days post-stroke.

DM199 met primary safety and tolerability endpoints and no DM199-related serious adverse events were noted in the study. According to top-line phase II results, there was also a demonstrated therapeutic effect in participants who received tissue plasminogen activator (tPA) prior to enrollment, but not in participants receiving mechanical thrombectomy.

"We are very excited about the positive top-line results which continue to demonstrate the excellent safety profile of DM199 and efficacy signals which are consistent with the approval study for Kailikang, the urine-derived form of KLK1 which has been used to successfully treat stroke patients in China for years," stated Rick Pauls, DiaMedica’s President and CEO. "These results strengthen our belief that DM199 can be a valuable treatment option for stroke victims, improving outcomes while providing a significantly longer, up to 24 hours, after onset of the stroke. We look forward to discussing a path to commercialization with the FDA."

DM199 for the Treatment of Chronic Kidney Disease

Phase II Clinical Study in CKD Caused by IgA Nephropathy and in African Americans with Hypertension – Enrollment Continues

The Phase II REDUX (latin for restore) trial is a multi-center, open-label investigation of approximately 60 participants with chronic kidney disease (CKD), who are being enrolled in two cohorts (30 per cohort). The study is ongoing in the United States at 12 sites and targets participants with CKD: Cohort I is enrolling non-diabetic, hypertensive African Americans with Stage II or III CKD, a group which is at greater risk for CKD than Caucasians. African Americans who have the APOL1 gene mutation are at an even higher risk. The study is designed to capture the APOL1 gene mutation as an exploratory biomarker in this cohort. Cohort II is enrolling participants with IgA Nephropathy (IgAN). The overall study evaluates two dose levels of DM199. Study participants in each cohort will receive DM199 by subcutaneous injection twice weekly for 95 days. The primary study endpoints include safety, tolerability, blood pressure, proteinuria and kidney function, which will be evaluated by changes from baseline in estimated glomerular filtration rate (eGFR) and albuminuria, as measured by the urinary albumin to creatinine ratio (UACR).

Due to actions implemented to combat the novel strain of the coronavirus (COVID-19) pandemic, the Company is experiencing slower than expected enrollment in the REDUX clinical study as activities are reduced or suspended at the clinical study sites as they address staff and patient safety concerns.The Company currently expects a delay in the timing of costs incurred as a result of the COVID-19 pandemic, but not a significant overall increase. The Company will continue to assess the effect of the pandemic on its REDUX trial by monitoring the spread of the COVID-19 virus and the actions implemented to combat the virus.

"Our highest priority right now is to protect the safety of subjects and clinical staff participating in the REDUX trial, and we believe that we have accomplished that" commented Dr. Harry Alcorn, DiaMedica’s Chief Medical Officer. "While enrollment has significantly slowed, we believe that the measures taken will allow our study to resume more normal rates of enrollment as COVID-19 related restrictions are eased."

Public Offering of Common Shares

On February 13, 2020, the Company issued and sold an aggregate of 2,125,000 common shares in a public, underwritten offering at a public offering price of $4.00 per share. As a result of the offering, the Company received gross proceeds of $8.5 million and net proceeds of $7.7 million, after deducting the underwriting discount and offering expenses.

Financial Results

Research and development (R&D) expenses were $1.4 million for the three months ended March 31, 2020, compared with $2.6 million for the three months ended March 31, 2019, a decrease of $1.2 million. The decrease was due to costs incurred during the first quarter of 2019 which did not reoccur during the first quarter of 2020, primarily the costs for a production run of the DM199 drug substance and the Phase Ib study in CKD patients. Declining costs for the ReMEDy study in the current year period also contributed to the decrease. These decreases were partially offset by costs incurred for the REDUX study, which began enrollment in December 2019, and increased non-cash share-based compensation costs.

General and administrative (G&A) expenses were $1.0 million for the three months ended March 31, 2020, up from $814,000 for the three months ended March 31, 2019. The increase in G&A expenses resulted primarily from increased non-cash share-based compensation costs.

Total other (income) expense, net, for the three months ended March 31, 2020 was a net expense of $12,000, compared with net income of $178,000 for the three months ended March 31, 2019. The change was primarily caused by the foreign currency transaction losses associated with funds held in non-functional currency (US dollar) accounts, principally Australian dollars. A decrease in R&D incentives, associated with decreased ReMEDy costs and reductions in interest income earned on marketable securities during the three months ended March 31, 2020, also contribute to this change.

Balance Sheet and Cash Flow

The Company had cash, cash equivalents and marketable securities of $12.6 million, current liabilities of $0.9 million and working capital of $13.2 million as of March 31, 2020, compared to $7.9 million in cash, cash equivalents and marketable securities, $1.3 million in current liabilities and $7.5 million in working capital as of December 31, 2019. The increases in the Company’s combined cash, cash equivalents and marketable securities and in its working capital are due primarily to the February 2020 public offering of common shares.

Net cash used in operating activities was $3.0 million for the three months ended March 31, 2020, compared to $3.1 million for the three months ended March 31, 2019. The net cash used in each of these periods primarily reflects the net loss for these periods, offset by non-cash charges for stock-based compensation and adjusted for the net effects of changes in operating assets and liabilities.

Conference Call Information

DiaMedica Management will host a conference call to discuss both its first quarter 2020 financial results and the top-line results from its ReMEDy study on Thursday, May 14, 2020, at 7:00 a.m. Central Time:

Date:

Thursday, May 14, 2020

Time:

7:00 AM CT / 8:00 AM ET

Web access:

View Source

Dial In:

(833) 502-0492 (domestic)

(778) 560-2558 (international)

Conference ID:

8757888

Interested parties may access the conference call by dialing in or listening to the simultaneous webcast. Listeners should log on to the website or dial in 15 minutes prior to the call. The webcast will remain available for play back on DiaMedica’s website, under investor events and presentations, following the earnings call and for 12 months thereafter. A telephonic replay of the conference call will be available until May 21, 2020, by dialing (800) 585-8367 (US Toll Free), (416) 621-4642 (International), replay passcode 8757888.

About DM199

DM199 is a recombinant (synthetic) form of the human serine protease, KLK1. The KLK1 protein plays an important role in the regulation of diverse physiological processes including blood flow, inflammation, fibrosis, oxidative stress and neurogenesis via a molecular mechanism that increases production of nitric oxide and prostaglandin. KLK1 deficiency may play a role in multiple vascular and fibrotic diseases such as chronic kidney disease, retinopathy, stroke, vascular dementia, and resistant hypertension where current treatment options are limited or ineffective. DiaMedica is the first company to have developed a recombinant form of the KLK1 protein. The KLK1 protein, produced from porcine pancreas and human urine, has been used to treat patients in Japan, China and Korea for decades. DM199 is currently being studied in patients with chronic kidney disease and patients with acute ischemic stroke.

On May 13, 2020 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported preliminary results from two of its investigational pipeline molecules (Press release, MacroGenics, MAY 13, 2020, View Source [SID1234557925]). Data covering safety and preliminary anti-tumor activity from the Phase 1 dose escalation and expansion clinical trial of MGD013, a bispecific, tetravalent DART molecule binding PD-1 and LAG-3, and the Phase 1 dose expansion study of MGC018, an antibody-drug conjugate (ADC) targeting B7-H3, will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) upcoming ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program to be held May 29-31, 2020.

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"We are encouraged by the early demonstration of activity of MGD013, our PD-1 x LAG-3 DART molecule, particularly in combination with margetuximab, our investigational Fc-engineered monoclonal antibody targeting HER-2, where preliminary observations in a Phase 1 trial suggest a response in approximately 40% of late-stage HER-2-positive tumors that compares favorably to low response rates for HER-2-directed agents and checkpoint blockade reported historically. Our rationale for combining MGD013 and margetuximab is based on early scientific insights that antibody Fc-engineering could potentially activate immune effector cells, resulting in upregulation of checkpoint molecules, such as LAG-3, PD-1 and PD-L1, which could be targeted for blockade by bispecific DART molecules like MGD013," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "Separately, we are also very encouraged by early results from an ongoing Phase 1 study of MGC018, an ADC directed against B7-H3, a molecule highly expressed on solid tumors and associated with poor clinical outcome. In this dose-escalation study, we have observed preliminary signals of anti-tumor effects, including prostate-specific antigen, or PSA, reductions of 50% or more in five of seven patients with late-stage prostate cancer."

Summary of Selected ASCO (Free ASCO Whitepaper) Presentations

"A phase I, first-in-human, open-label, dose-escalation study of MGD013, a bispecific DART molecule binding PD-1 and LAG-3, in patients with unresectable or metastatic neoplasms" (Abstract #3004)

MGD013 is designed to independently or coordinately block PD-1 and LAG-3 checkpoint molecules to sustain or restore the function of exhausted T cells for the treatment of cancer. In the dose-escalation part of the study, 53 patients with advanced tumors were treated with MGD013 given intravenously in cohorts of escalating flat doses of 1-1200 mg every two weeks. A maximum tolerated dose was not identified. A flat dose of 600 mg every two weeks was selected for tumor-specific expansion cohorts. At the April 25, 2020 data cut-off, 205 patients with advanced solid and hematologic neoplasms have been treated with MGD013 monotherapy in the ongoing dose-expansion part of the study, of which 152 were evaluable for response. An additional 21 patients with advanced HER2-positive tumors, including 14 who were evaluable for response, were treated with the combination of margetuximab, an investigational Fc-engineered monoclonal antibody targeting HER-2, at 15 mg/kg and MGD013 at flat doses of 300 mg or 600 mg, both given every three weeks. Anti-tumor activity was assessed by Response Evaluation Criteria in Solid Tumors (RECIST). For more information about the study design, please visit ClinicalTrials.gov (NCT03219268).

The overall safety profile of MGD013 in the Phase 1 study, including the incidence of immune-mediated adverse events, appears generally consistent with anti-PD-1 antibody monotherapy with respect to event type and frequency. Anti-tumor activity of MGD013 as monotherapy has been observed in evaluable patients across several of the tumor types in the selected dose expansion cohorts. Objective response rates (ORR), including both confirmed and unconfirmed responses, and disease control rates (DCR), comprising both confirmed objective responses and stable disease, were observed as follows: triple negative breast cancer (17% ORR, 4 of 23 patients; 39% DCR, 9 of 23 patients), epithelial ovarian cancer (9% ORR, 2 of 23 patients; 52% DCR, 12 of 23 patients) and non-small cell lung cancer (checkpoint inhibitor naïve: 21% ORR, 3 of 14 patients; 64% DCR, 9 of 14 patients; and post anti-PD-1: 13% ORR, 2 of 15 patients; 53% DCR, 8 of 15 patients). Response to MGD013 monotherapy was associated with LAG-3 expression and an IFN-γ gene signature at baseline.

Immune effector cell activation and LAG-3, PD-1 and PD-L1 expression are enhanced in vitro by Fc-engineered margetuximab. An expansion cohort of patients with advanced HER2-positive tumors is being treated with margetuximab plus MGD013 to evaluate whether Fc-engineering can enhance tumor responsiveness to checkpoint blockade and improve clinical outcomes in patients. Objective responses were observed in 6 of 14 (43%) evaluable patients treated with margetuximab and MGD013, of which four have been confirmed, with tumor-shrinkage observed in other patients. Responses were observed in patients with a range of relapsed or refractory HER2-positive tumor types. In contrast with the monotherapy finding, in the combination cohort, the majority of responders whose baseline tumors were evaluated were negative for (or expressed low levels of) LAG-3 or PD-L1. All responders remain on therapy.

These results and additional details will be presented during an oral session titled: Developmental Therapeutics—Immunotherapy.

"Preliminary dose escalation results from a phase I/II, first-in-human study of MGC018 (anti-B7-H3 antibody-drug conjugate) in patients with advanced solid tumors" (Abstract #3071, Poster #135)

MGC018 is designed to deliver a DNA alkylating duocarmycin payload to dividing and non-dividing cells that express B7-H3, a ligand that is highly expressed on many solid tumors and is associated with a poor clinical outcome. At the May 6, 2020 data cut-off, 23 patients with advanced solid tumors had been enrolled in four dose escalation cohorts of 0.5 mg/kg to 3 mg/kg given intravenously every three weeks. Enrollment is ongoing in a fifth cohort at 4 mg/kg every three weeks. For information about the study design, please visit ClinicalTrials.gov (NCT03729596).

The safety profile of MGC018, which includes hematologic and skin toxicities, has been generally manageable to date. At least one treatment related adverse event occurred in 22 of 24 patients (92%), including Grade ≥3 reported in 14 of 24 patients (58%). Three treatment-related serious adverse events occurred in one patient each: pneumonitis in a patient with concurrent bacterial pneumonia; non-infectious gastroenteritis; and stasis dermatitis in a patient with chronic venous insufficiency. One dose-limiting toxicity of Grade 4 neutropenia that resolved to baseline was reported​. No febrile neutropenia was observed.

Preliminary evidence of anti-tumor activity by MGC018 has been observed, particularly in patients with advanced metastatic castration-resistant prostate cancer (mCRPC). Reductions in PSA levels of ≥50% were observed in five of seven mCRPC patients treated, including one with substantial regression of bone disease. Six mCRPC patients had bone only disease, and one patient with measurable peripheral disease had a 29% reduction in target lesions that did not qualify as a response per RECIST. Four PSA responders remain on therapy. Patients with mCRPC had received a median of four therapies prior to MGC018, including taxane chemotherapy (six patients) and next generation hormonal agents (six patients were treated with both abiraterone and enzalutamide, and one with abiraterone only).

These results and additional details will be presented during a poster session titled: Developmental Therapeutics—Immunotherapy.

ASCO Virtual Presentations

Abstracts for these presentations submitted in February 2020 are available on the ASCO (Free ASCO Whitepaper) website at www.asco.org. Presentations will be available for on-demand viewing online at View Source beginning on May 29, 2020 at 8:00 a.m. ET.

The static slides and poster will be available on the Events & Presentations page on MacroGenics’ website at View Source

On May 13, 2020 Legend Biotech Corporation ("Legend") reported updated results from the Janssen Pharmaceutical Companies of Johnson & Johnson ("Janssen") sponsored Phase 1b/2 CARTITUDE-1 study (NCT03548207)1 evaluating the efficacy and safety of JNJ-68284528 (JNJ-4528), an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapy in the treatment of patients with relapsed or refractory multiple myeloma (Press release, Legend Biotech, MAY 13, 2020, View Source [SID1234557942]). JNJ-4528 is a structurally differentiated CAR-T cell therapy containing a 4-1BB co-stimulatory domain and two BCMA-targeting single-domain antibodies designed to confer avidity.2

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Longer-term follow-up results from the Phase 1b portion of the study (n=29), to be shared in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Program (Abstract #8505), show that all patients responded to treatment and that the responses were deep and durable with 86 percent of patients achieving stringent complete response at a median follow-up time of 11.5 months. In addition, results showed a 100 percent overall response rate (ORR), which included 97 percent of patients achieving a very good partial response or better and three percent achieving a partial response. The median time to first response was one month (range, 1-3), and 81 percent of evaluable patients (n=16) achieved minimal residual disease (MRD)-negative disease status at 10-5 or 10-6 at the time of first suspected complete response. The 9-month progression free survival rate was 86 percent and 22 of 29 patients remained alive and progression free at the time of data cut-off. Patients in the study were heavily pre-treated and received a median dose of 0.72×106 CAR+ viable T cells/kg.3

Patients evaluated received a median of five (range, 3-18) prior treatment regimens; 86 percent were triple-refractory and 28 percent were penta-refractory.

"The longer-term results for JNJ-4528, as demonstrated through the latest findings from the CARTITUDE-1 study, show the continued treatment effect for heavily pre-treated patients who faced a poor prognosis," said Jesus G. Berdeja, M.D., Director of Myeloma Research, Sarah Cannon Research Institute, and principal study investigator. "We’re encouraged by not only the relatively high rate of stringent complete responses, but the strong progression-free survival results seen in these patients."

The most common adverse events (AEs) observed in CARTITUDE-1 were neutropenia (100 percent) and cytokine release syndrome (CRS) (93 percent). The median time to onset of CRS was seven days (range, 2-12) post-infusion, with a majority of patients experiencing Grade 1-2 CRS and two patients experiencing Grade 3 or greater CRS. In patients who experienced Grade 3 and above AEs, the most common were neutropenia (100 percent), thrombocytopenia (69 percent), and leukopenia (66 percent). Neurotoxicity consistent with ICANS was observed in 3 patients (10 percent) including 1 patient (3 percent) with ≥ Grade 3 toxicity. There were 3 deaths during the Phase 1b study: one due to CRS, one due to acute myeloid leukemia (not treatment-related), and one due to progressive disease.3

"We are heartened by the follow-up data from the Phase 1b portion of the CARTITUDE-1 study as they further support the findings from the LEGEND-2 study in China, with both demonstrating deep, durable treatment responses," said Yuan Xu, PhD, Chief Executive Officer and Board Member of Legend Biotech. "We remain committed to work closely with our strategic partner and key stakeholders to advance JNJ-4528 through clinical development, in line with our mission to deliver innovative cell therapy options to patients living with cancer."

About CARTITUDE-1

CARTITUDE-1 (NCT03548207) is an ongoing Phase 1b/2, open-label, multicenter study evaluating the safety and efficacy of JNJ-4528 in adults with relapsed or refractory multiple myeloma. Of the patients in the Phase 1b portion (n=29), 97 percent were refractory to last line of treatment and 86 percent were triple-class refractory, meaning their cancer did not respond to an immunomodulatory agent (IMiD), a proteasome inhibitor (PI) and an anti-CD38 antibody.

The primary objective of the Phase 1b portion of the study was to characterize the safety and confirm the dose of JNJ-4528, informed by the first-in-human study with LCAR-B38M CAR-T cells (LEGEND-2). Based on the safety profile observed in this portion of the study, outpatient dosing will be evaluated in additional CARTITUDE studies. The Phase 2 portion of the study will evaluate the efficacy of JNJ-4528 with overall response as the primary endpoint.

About JNJ-4528 (LCAR-B38M)

JNJ-4528 (LCAR-B38M) is an investigational CAR-T therapy for the treatment of patients with RRMM. The design comprises a structurally differentiated CAR-T with two BCMA-targeting single domain antibodies.

JNJ-4528 identifies the investigational product being studied in the US, Europe, and Japan. LCAR-B38M identifies the investigational product being studied in China. Both represent the same CAR-T cell therapy.

In December 2017, Legend Biotech, USA Inc., and Legend Biotech Ireland Limited, entered into a worldwide collaboration and license agreement with Janssen, to jointly develop and commercialize JNJ-4528/LCAR-B38M in multiple myeloma.

In May 20184, Legend announced that the U.S. Food and Drug Administration (FDA) authorized Janssen to initiate a Phase 1b/2 trial (NCT03548207)1 to evaluate the efficacy and safety of JNJ-4528 in adults with RRMM, informed by the LEGEND-2 (NCT03090659)5 study results.

In December 20196, Legend announced that the FDA granted Janssen Breakthrough Therapy Designation, which is granted to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition.7 In February 20198, the U.S. FDA granted Janssen an Orphan Drug Designation for JNJ-4528. In April 20199, JNJ-4528 was granted PRIME (PRIority MEdicines) designation by the European Medicines Agency (EMA). PRIME offers enhanced interaction and early dialogue to optimize development plans and speed up evaluation of cutting-edge, scientific advances that target a high unmet medical need.10 In February 2020, the European Commission granted Janssen an Orphan Drug Designation for JNJ-4528.11

About Multiple Myeloma

Multiple myeloma is currently an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.12 Although treatment may result in remission, patients will most likely relapse as there is currently no cure.13 Refractory multiple myeloma is when a patient’s disease is nonresponsive or progresses within 60 days of their last therapy.14,15 Relapsed myeloma is when the disease has returned after a period of initial, partial or complete remission and does not meet the definition of being refractory.16 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.17 Patients who relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents, have poor prognoses and few treatment options available.18

On May 13, 2020 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) reported the financial results and corporate updates for the first quarter 2020 (Press release, Evotec, MAY 13, 2020, View Source;announcements/press-releases/p/evotec-se-reports-first-quarter-2020-results-and-provides-corporate-update-5939 [SID1234557960]).

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HIGHLIGHTS

STRONG PERFORMANCE IN BASE BUSINESS; INCREASED REVENUES DESPITE MODEST MILESTONE CONTRIBUTIONS IN Q1
15% increase in group revenues from contracts with customers to € 119.4 m (Q1 2019: € 103.8 m)
Strong revenue growth in both segments: EVT Execute revenues up 18% to € 118.2 m (Q1 2019: € 100.3 m), EVT Innovate revenues up 24% to € 23.3 m (Q1 2019: € 18.8 m)
Stable adjusted Group EBITDA of € 30.0 m (Q1 2019: € 30.0 m); adjusted EBITDA of € 35.4 m for EVT Execute (Q1 2019: € 32.2 m)
Increased commitment into unpartnered R&D with expenses of € 11.4 m (Q1 2019: € 8.1 m)
Continued strong strategic liquidity position of € 320.7 m (31 December 2019: € 320.0 m)
No material impact by COVID-19 pandemic on financial development so far

EVT EXECUTE & EVT INNOVATE – STRONG PERFORMANCE AND STRATEGIC POSITION IN BOTH BUSINESS SEGMENTS
Important step into gene therapy with Evotec GT and multi-year gene therapy research alliance with Takeda
New and extended drug discovery and development agreements in EVT Execute (e.g. Amgen, Ildong)
Just – Evotec Biologics on track for success: Strengthened position through first strategic J.POD partnership with MSD and continued good construction progress of the first J.POD facility in Seattle
Advancement of an additional endometriosis programme into clinical Phase I within Bayer alliance, triggering a € 2 m milestone payment
Strengthening of Evotec’s iPSC-based cell therapy platform EVOcells through licensing agreement with panCELLa
Regaining global rights on iPSC-based beta cell replacement therapy from Sanofi and initiation of EVT Innovate initiative QRbeta Therapeutics (after period-end)
Strategic equity investment and partnership with leon-nanodrugs expands formulation platform
Evotec contributing to selected global initiatives to fight Tuberculosis and COVID-19

GUIDANCE FOR FULL-YEAR 2020 CONFIRMED
Unchanged business outlook, taking into account currently visible negative COVID-19 effects
Total group revenues expected to range from € 440 – 480 m (2019: € 446.4 m)
Adjusted Group EBITDA expected to be in the range of € 100 – 120 m (2019: € 123.1 m)
Unpartnered Group R&D expenses of approx. € 40 m

More detailed information and financial tables are available in our Quarterly Statement Q1 published on the Evotec website under the following link: View Source

Webcast/Conference Call
The Company is going to hold a conference call to discuss the results as well as to provide an update on its performance in the reporting period. Furthermore, the Management Board will present an outlook for fiscal year 2020. The conference call will be held in English.

Conference call details

Date: Thursday, 14 May 2020

Time: 02.00 pm CEST (08.00 am EDT, 01.00 pm BST)

A simultaneous slide presentation for participants dialling in via phone is available at View Source

Webcast details

To join the audio webcast and to access the presentation slides you will find a link on our home page shortly before the event.

A replay of the conference call will be available for seven days after the conference and can be accessed in Europe by dialling +49 69 20 17 44 221 (Germany) or +44 20 3364 5150 (UK) and in the USA by dialling +1 844 307 9362. The access code is 315586222#. The on-demand version of the webcast will be available on our website under View Source