On August 4, 2020 Oncopeptides AB (publ) (Nasdaq Stockholm: ONCO) reported that the first patient has been enrolled in the phase 2 PORT study (Press release, Oncopeptides, AUG 4, 2020, View Source [SID1234562750]). The study, which is expected to be fully recruited in December 2020, is an open-label, randomized, cross-over study which compares safety, tolerability and efficacy of peripheral or central intravenous administration of melflufen in combination with dexamethasone in patients with relapsed refractory multiple myeloma, RRMM. Up to 25 RRMM patients who have received at least two previous lines of therapy will be enrolled.

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"Patients who receive anti-cancer treatment often get an implanted port, a type of central venous catheter placed under the skin, to limit the number of needle sticks, facilitate intravenous administration and enhance convenience. The PORT study may provide an additional option in the way melflufen is delivered", says Klaas Bakker, CMO of Oncopeptides. "Broadening the mode of administration would allow physicians to choose the option that is preferable for their patients".
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 persons above, on August 4, 2020 at 15.30 (CET).

About melflufen
Melflufen (INN melphalan flufenamide) is a first in class peptide-drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. Melflufen is rapidly taken up by myeloma cells due to its high lipophilicity and is immediately hydrolyzed by peptidases to release an entrapped hydrophilic alkylator payload. Peptidases play a key role in protein homeostasis and feature in cellular processes such as cell-cycle progression and programmed cell death. In vitro, melflufen is 50-fold more potent in myeloma cells than the alkylator payload itself due to the increased intracellular alkylator concentration. 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. In the pivotal phase 2 HORIZON study melflufen plus dexamethasone demonstrated encouraging efficacy and a clinically manageable safety profile in heavily pretreated patients with relapsed refractory multiple myeloma, with primarily hematologic Adverse Events (AE) and a low incidence of non-hematologic AEs.

On August 4, 2020 Avelas Biosciences, Inc., pioneering the field of intraoperative fluorescent cancer imaging, reported positive top-line data demonstrating that the company’s recently completed Phase 2/3 registration study of the use of pegloprastide (AVB-620) during surgery met its primary endpoint of detecting cancer in margin specimens in real time (p<0.001) (Press release, Avelas Biosciences, AUG 4, 2020, View Source [SID1234562749]). Pegloprastide is designed to deliver a fluorescent marker specifically to cancer cells for surgeons to identify cancerous tissue in real-time to reduce repeat surgeries and improve patient outcomes. The pivotal study evaluated the safety and efficacy of pegloprastide in women with primary, nonrecurrent breast cancer undergoing surgery. In more than 150 patients dosed to date, no drug-related serious adverse events were reported.

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"With pegloprastide, we are removing the blindfold and helping surgeons see where the cancer is to make informed, real-time decisions in the operating room," said Jay Lichter, Ph.D., Chairman, President, and Chief Executive Officer of Avelas. "This pivotal clinical data is a first in the field of fluorescence image-guided surgery for breast cancer and supports the use of pegloprastide to revolutionize surgical treatment with the goal of eliminating tens of thousands of repeat surgeries undertaken to address positive margins."

The presence of positive margins is a significant challenge in breast-conserving surgery. Positive surgical margins occur when post-operative pathology indicates cancer cells are present at the edge of removed tissue, indicating that not all the malignant tissue was removed during an operation. It is estimated that each year in the United States more than 260,000 women undergo a lumpectomy, of which one-third (more than 80,000) are repeat surgeries with the goal of achieving negative margins.1 Beyond that, of the estimated 90,000 women who choose a mastectomy, many choose it for fear of incomplete initial lumpectomy.1

"Cancer recurrence and metastasis is more likely with positive margins, and the significant re-excision rate with standard of care for lumpectomies to try to obtain negative margins is driving women to get second lumpectomies, causing significant pain and physical limitations," said Sheldon M. Feldman, M.D., chief, division of breast surgery and surgical oncology, and director, Breast Cancer Services at Montefiore Einstein Center for Cancer Care and professor of surgery, Albert Einstein College of Medicine. "Pegloprastide has the potential to greatly improve a breast surgeon’s ability to achieve negative margins and reduce the number of re-excisions, potentially improving outcomes for hundreds of thousands of women and saving thousands of lives."

Top-line data showed the planned re-excision rate for patients who underwent breast cancer surgery with pegloprastide was 6%, much lower than the typical re-excision rate of 20-40%.2-7 For the study, surgeons first excised the tumor using standard of care methods followed by interoperative imaging of both the excised tissue and the surgical site using pegloprastide and a specialized fluorescent imaging device manufactured for Avelas by Quest Medical Imaging, based on its QUEST SPECTRUM platformtechnology. With pegloprastide, 75% of the patients, who still had positive margins, were able to be identified.

Steven Chen, M.D., Chief Medical Officer of Avelas Biosciences, said, "Today, in an era of patient-centered care, high re-excision rates need to become a historical artifact. This data indicates that pegloprastide could significantly reduce the need for these repeat breast cancer surgeries driven by positive margins. We are grateful to our clinical collaborators and especially to the patients who participated in this pivotal trial as we advance pegloprastide to meaningfully improve surgical outcomes for breast cancer and beyond."

The primary endpoint of Period 2 of the pivotal study was the ability to detect cancer in margin-relevant tissue, using pegloprastide fluorescence imaging, in sufficient number of patients to demonstrate efficacy; this was achieved with high statistical significance (p-value < 0.001). The secondary endpoint of intraoperative patient-level cancer detection performance in margin-relevant tissue, using prespecified thresholds, indicated that up to 75% of patients that would have had a positive margin could benefit from this investigation product at a statistically significant level. During the trial, patients were administered pegloprastide either the day before surgery or the day of surgery; initial data supports pegloprastide administration the day before the surgery as the preferred dosing time. Other secondary and exploratory endpoints included false positives, specimen and sample type detection, and planned re-excisions. All showed strong indications supporting efficacy and utility of pegloprastide. The study showed no serious adverse events or laboratory abnormalities attributable to the infusion of pegloprastide.

About the Phase 2/3 Trial

The pivotal Phase 2/3 study of pegloprastide was a multi-center, open-label, single-arm study designed to evaluate patients during two separate trial periods. Period 1, which was completed in December 2017, enrolled 32 patients and demonstrated proof-of-concept that pegloprastide could sensitively visualize the primary tumor in the lumpectomy specimen. In addition, optimal dosing and imaging conditions, including fluorescent thresholds, to achieve differentiation between malignant and nonmalignant tissue in margin-relevant tissue was determined. Period 2, which is expected to be a registration study, was completed in March 2020 and enrolled 92 additional patients to prospectively assess the ability of pegloprastide to identify malignant tissue at or close to the surface of excised tissue and of tissue that would otherwise have been left behind and require a reoperation to remove. Both study periods enrolled women with the most common breast cancer types – DCIS (Stage 0) and/or Stage I-III invasive carcinoma – with all grades (Grades 1-3) and all receptor statuses. Imaging of pegloprastide was performed on all types of tissue, including excised specimen, cavity shaves, and residual tissue left in the surgical cavity.For more information, visit www.clinicaltrials.gov.

About Pegloprastide (AVB-620) and QUEST SPECTRUM Fluorescent Imaging Device

Pegloprastide (AVB-620) is based on the science of activatable cell-penetrating peptides and is the only fluorescence-based clinical cancer detection product that uses the ratio of two fluorophores within the same molecule (ratiometric imaging) to provide more accurate and actionable information. Pegloprastide’s ratiometric readout attenuates common artifacts of fluorescent imaging, including differences in drug concentration and distance of the camera from the tissue area of interest. QUEST SPECTRUM device has a wide field of view (~10 cm) and provides a rapid assessment of tissue (~100 ms). Beyond breast cancer, Avelas has plans to explore the use of pegloprastide during surgery for other types of cancer, including ovarian, colorectal, head and neck, melanoma, and sarcoma.

On August 4, 2020 Novartis reported positive results from the Phase II ELARA trial of Kymriah (tisagenlecleucel) in patients with relapsed or refractory (r/r) follicular lymphoma (FL) (Press release, Novartis, AUG 4, 2020, View Source [SID1234562744]). At the interim analysis, the global study met its primary endpoint of complete response rate (CRR), as assessed by independent review committee. CRR is a standard measure of patient response to therapy in FL. No new Kymriah safety signals were observed. Results from the ELARA trial will be presented at an upcoming medical meeting and included in US and EU regulatory submissions.

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Kymriah was the first-ever FDA-approved CAR-T cell therapy, and the first-ever CAR-T to be approved in two distinct indications. It is a one-time treatment designed to empower patients’ immune systems to fight their cancer. Kymriah is currently approved for the treatment of r/r pediatric and young adult (up to 25 years of age) acute lymphoblastic leukemia (ALL), and r/r adult diffuse large B-cell lymphoma (DLBCL)1.

"We are pleased that Kymriah is showing meaningful results and may provide a potentially definitive treatment option for patients with relapsed and refractory follicular lymphoma," said John Tsai, MD, Head of Global Drug Development and Chief Medical Officer, Novartis. "These results further support our efforts to reimagine medicine in this incurable malignancy and reach this underserved patient population, who are historically burdened with several years of various treatments."

Kymriah was developed in collaboration with the Perelman School of Medicine at the University of Pennsylvania, a strategic alliance between industry and academia, which was first-of-its-kind in CAR-T research and development.

Kymriah is currently approved for use in at least one indication in more than 25 countries and at more than 250 certified treatment centers, with the ambition for further expansion to help fulfill the ultimate goal of bringing CAR-T cell therapy to every patient in need. As Novartis prepares for the launch of a potential third indication for Kymriah, manufacturing capacity continues to ramp up. The Novartis global CAR-T manufacturing footprint spans seven facilities total, across four continents. This comprehensive, integrated footprint strengthens the flexibility, resilience and sustainability of the manufacturing and supply chain. With recent approvals from the European Medicines Agency (EMA), commercial manufacturing of Kymriah is now ongoing at the Novartis-owned facilities in Stein, Switzerland and Les Ulis, France, joining the Novartis-owned facility in Morris Plains, New Jersey, USA.

About Follicular Lymphoma
Follicular lymphoma, the second most common form of non-Hodgkin lymphoma (NHL), is an indolent lymphoma, and represents approximately 22% of NHL cases2,3. Despite new treatments that improve overall survival, FL is regarded as an incurable malignancy with a relapsing and remitting pattern4,5. Throughout the lifetime of a patient with relapsing FL, they may be exposed to a median of five lines of prior treatment, with an upper range of 12 lines6,7. Although patients in third or later line treatment for FL have multiple systemic therapies available, the efficacy of these regimens drops off rapidly in later lines5. Additionally, because of this relapsing and remitting pattern, patients who are refractory to treatment or quickly relapse may exhaust available treatment options5.

About the ELARA trial
ELARA is a Phase II, single-arm, multicenter, open-label trial investigating the efficacy and safety of Kymriah in adult patients with r/r FL. This international trial has enrolled patients from over 30 sites in 12 countries worldwide.

In Q2 2020, the FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to Kymriah in r/r FL, based on preliminary results from the ELARA trial. RMAT designation is intended to expedite the development and review of Kymriah as a regenerative therapy for this underserved patient population.

About Novartis Commitment to Oncology Cell & Gene
Novartis has a mission to reimagine medicine by bringing curative cell & gene therapies to patients worldwide. Novartis has a deep CAR-T pipeline and ongoing investment in manufacturing and supply chain process improvements. With active research underway to broaden the impact of cell therapy in oncology, Novartis is going deeper in hematological malignancies, reaching patients with other cancer types and evaluating next-generation CAR-T cell therapies that focus on new targets and utilize new technologies.

Novartis was the first pharmaceutical company to significantly invest in pioneering CAR-T research and initiate global CAR-T trials. Kymriah, the first approved CAR-T cell therapy, developed in collaboration with the Perelman School of Medicine at the University of Pennsylvania, is the foundation of Novartis’ commitment to CAR-T cell therapy.

Kymriah (tisagenlecleucel) US Important Safety information
Kymriah may cause side effects that are severe or life-threatening, such as Cytokine Release Syndrome (CRS) or Neurological Toxicities. Patients with CRS may experience symptoms including difficulty breathing, fever (100.4°F/38°C or higher), chills/shaking chills, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, or dizziness/lightheadedness. Patients may be admitted to the hospital for CRS and treated with other medications.

Patients with neurological toxicities may experience symptoms such as altered or decreased consciousness, headaches, delirium, confusion, agitation, anxiety, seizures, difficulty speaking and understanding, or loss of balance. Patients should be advised to call their healthcare provider or get emergency help right away if they experience any of these signs and symptoms of CRS or neurological toxicities.

Because of the risk of CRS and neurological toxicities, Kymriah is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called Kymriah REMS.

Serious allergic reactions, including anaphylaxis, may occur after Kymriah infusion. Kymriah can increase the risk of life-threatening infections that may lead to death. Patients should be advised to tell their healthcare provider right away if they develop fever, chills, or any signs or symptoms of an infection.

Patients may experience prolonged low blood cell counts (cytopenia), where one or more types of blood cells (red blood cells, white blood cells, or platelets) are decreased. The patient’s healthcare provider will do blood tests to check all of their blood cell counts after treatment with Kymriah. Patients should be advised to tell their healthcare provider right away if they get a fever, are feeling tired, or have bruising or bleeding.

Patients may experience hypogammaglobulinemia, a condition in which the level of immunoglobulins (antibodies) in the blood is low and the risk of infection is increased. It is expected that patients may develop hypogammaglobulinemia with Kymriah, and may need to receive immunoglobulin replacement for an indefinite amount of time following treatment with Kymriah. Patients should tell their healthcare provider about their treatment with Kymriah before receiving a live virus vaccine.

After treatment with Kymriah, patients will be monitored lifelong by their healthcare provider, as they may develop secondary cancers or recurrence of their cancer.

Patients should not drive, operate heavy machinery, or do other dangerous activities for eight weeks after receiving Kymriah because the treatment can cause temporary memory and coordination problems, including sleepiness, confusion, weakness, dizziness, and seizures.

Some of the most common side effects of Kymriah are difficulty breathing, fever (100.4°F/38°C or higher), chills/shaking chills, confusion, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, dizziness/lightheadedness, and headache. However, these are not all of the possible side effects of Kymriah. Patients should talk to their healthcare provider for medical advice about side effects.

Prior to a female patient starting treatment with Kymriah, their healthcare provider may do a pregnancy test. There is no information available for Kymriah use in pregnant or breast-feeding women. Therefore, Kymriah is not recommended for women who are pregnant or breast feeding. Patients should talk to their healthcare provider about birth control and pregnancy.

Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

After receiving Kymriah, patients should be advised that some commercial HIV tests may cause a false-positive test result. Patients should also be advised not to donate blood, organs, or tissues and cells for transplantation after receiving Kymriah.

On August 3, 2020 CorMedix Inc. (NYSE American: CRMD), a biopharmaceutical company focused on developing and commercializing therapeutic products for the prevention and treatment of infectious and inflammatory disease, reported that it will report its financial results for the second quarter ended June 30, 2020, after the market close on Monday, August 10, and will host a corporate update conference call at 4:30pm Eastern Time (Press release, CorMedix, AUG 3, 2020, View Source [SID1234569342]).

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Monday, August 10th @ 4:30pm ET

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On August 3, 2020 Immodulon, the immuno-oncology company, and the Champalimaud Foundation, a private, non-profit, research organisation in Lisbon, Portugal, reported research intended to examine the potential use of IMM-101, in combination with other treatments, to achieve clinically favourable, anti-tumour directed cellular immune responses in advanced cancers including, but not limited to, pancreatic cancer, glioblastoma and sarcoma (Press release, Immodulon Therapeutics, AUG 3, 2020, View Source [SID1234565507]). The first studies are expected to commence in the second half of 2020.

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Dr. Jaap Kampinga, Chief Executive Officer of Immodulon, commented:
"We are thrilled to announce our collaboration with the Champalimaud Foundation. There is a clear unmet medical need for effective treatments against these devastating cancers. Despite the advent of immune checkpoint inhibitors, pancreatic cancer and sarcomas remain exceedingly challenging to treat, and novel combination treatments will be required to make progress in these cancers. The Champalimaud Foundation, as a centre of excellence, is well suited to researching such treatment regimens and to carry out these clinical studies. We are proud that the Champalimaud Foundation has selected IMM-101 as a backbone immunotherapy to develop novel personalised treatments, and we look forward to working further with this fantastic organisation."

Dr. Markus Maeurer, heading the Immunotherapy/Immunosurgery programme, noted:
"I am glad to be working together with the excellent Immodulon team. The quality and quantity of cellular immune responses in the biological therapy of cancer is key to achieving clinically relevant immune responses. Anti-cancer directed immune responses may exist in patients with cancer, yet they may become ineffective: they need to be ‘re-wired’. Newly elicited immune responses that specifically target cancer cells also need to have a certain quality and to be able to enter into the tumour tissue in order to be effective. Immodulon’s IMM-101 may help to bring us closer to achieve these goals based on available preclinical and clinical IMM-101 data and aid to design safe and
effective therapies for patients with cancer, particularly for patients with ‘difficult-to-treat-cancers’, such as pancreatic cancer. We hope – by implementing IMM-101 in our strategies – to be able to elicit ‘smarter’ immune responses that are more effective in eradicating cancer cells and in establishing long-term, protective immune memory."

‘Re-wiring’ immune responses – Personalised therapies for patients with cancer aim to direct immune cells against mutations, changes in the DNA, that are exclusively present in cancer cells, but not in healthy cells. If immune cells can be sufficiently activated and ‘trained’ to recognise these mutations, they may eliminate cancer cells without harming healthy tissue. These mutations, alterations in the genetic code, may be different for each individual patient.

Activation of immune cells needs an ‘alarm’ signal that activates and stimulates them to multiply. IMM-101 may help to provide this signal. However, this may not be sufficient in order to achieve a
relevant clinical effect: immune cells recognising cancer cells need to have a certain quality and produce molecules that are able to fight off and ultimately eradicate cancer cells. Nevertheless, this often is not possible for immune cells from patients with cancer: they have a reduced ‘fitness’, they are exhausted and are not able to eliminate cancer cells effectively.

IMM-101 may help to change this non-productive behaviour of the immune system, it may aid to ‘un-learn’ non-effective response patterns and correct immune exhaustion. Therefore, we hope that IMM-101 helps to correct several immune mechanisms that failed in patients with cancer and leads to activation of immune cells that target specifically cancer cells, correct immune exhaustion and increase ‘fitness’ in immune cells in order to fight against cancer more effectively.