On May 19, 2021 aTyr Pharma, Inc. (Nasdaq: LIFE), a biotherapeutics company engaged in the discovery and development of innovative medicines based on novel biological pathways, reported that it will present a poster and participate in a live Q&A session at the Virtual Keystone Symposia on Cancer Stem Cells: Advances in Biology and Clinical Translation, which is being held May 19 – 21, 2021 (Press release, aTyr Pharma, MAY 19, 2021, View Source [SID1234580294]). The abstract and poster are available on the Keystone Symposia website.

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The poster presents preclinical findings demonstrating that ATYR2810, a Neuropilin-2 (NRP2) antibody, selectively blocks the NRP2/VEGFR signaling axis and sensitizes patient-derived xenograft models of triple-negative breast cancer (TNBC) to chemotherapy. Furthermore, gene expression data from TNBC xenograft samples and patient derived organoids show that ATYR2810 downregulates several cancer stem cell and epithelial-mesenchymal transition (EMT) markers.

Details of the abstract and poster presentation are as follows:

Title: ATYR2810, a Neuropilin-2 antibody, selectively blocks the NRP2/VEGFR signaling axis and sensitizes aggressive cancers to chemotherapy
Authors: Yeeting E. Chong, Zhiwen Xu, Hira Lal Goel, Alison G. Barber, Christoph Burkart, Luke Burman, Kaitlyn Rauch, Justin Rahman, Arthur M. Mercurio, Leslie A. Nangle. aTyr Pharma, San Diego, CA, University of Massachusetts Medical School, Boston, MA.
Session: Poster Session 1
Live Q&A Date and Time: May 19, 2021, 2:30 – 3:00pm ET

The poster is also available on the aTyr website.

"We are very excited about these recent findings, which build upon our understanding of the mechanistic impact of blocking the NRP2/VEGF signaling axis with ATYR2810 on aggressive tumor cells and demonstrate the molecular basis for its selectivity by directly obstructing the VEGF binding site on NRP2," said Leslie Nangle, Ph.D., Vice President, Research at aTyr. "The research presented here, which includes data in patient-derived xenografts, suggests that ATYR2810’s ability to effect EMT and cancer stem cell properties may be one mechanism by which it mediates the anti-tumor effects we have observed. This work moves us closer to identifying the underlying characteristics within a tumor that may confer responsiveness to treatment with ATYR2810."

About ATYR2810

aTyr is developing ATYR2810 as a potential therapeutic for certain aggressive tumors where Neuropilin-2 (NRP2) is implicated. ATYR2810 is a fully humanized monoclonal antibody that is designed to specifically and functionally block the interaction between NRP2 and one of its primary ligands, VEGF. ATYR2810 is the first Investigational New Drug (IND) candidate to arise from aTyr’s in-house research program designing monoclonal antibodies to selectively target the NRP2 receptor and its associated signaling pathways. NRP2 is a cell surface receptor that is highly expressed in certain tumors, in the lymphatic system and on key immune cells implicated in cancer progression. Increased NRP2 expression is associated with worse outcomes in many cancers. Preclinical data suggest that ATYR2810 could be effective against certain types of solid tumors. ATYR2810 is currently undergoing IND-enabling studies.

On May 19, 2021 Bayer reported that it present new data across four distinct analyses showcasing the consistent, long-term clinical profile for Vitrakvi (larotrectinib) across TRK fusion cancer patients of all ages (range: 0.1-84 years) and multiple tumor types (Press release, Bayer, MAY 19, 2021, View Source [SID1234580310]). The analyses include updated long-term efficacy and safety data across solid tumors, including primary central nervous system (CNS) tumors and lung cancer, harboring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. In addition, an intra-patient pooled retrospective analysis assessing the treatment effect of Vitrakvi in patients with TRK fusion cancer previously treated with one or more line of therapy were presented. These analyses add to the existing clinical profile for Vitrakvi, which has the largest dataset and longest follow-up of any TRK inhibitor, at median follow-up of 22.3 months, for patients across all ages and tumor types with an NTRK gene fusion. These findings are being presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held online June 4-8, 2021.

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Vitrakvi is approved for the treatment of adult and pediatric patients with solid tumors that have an NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. Patients should be selected for therapy based on a Food and Drug Administration (FDA)-approved test. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1

"This data adds to larotrectinib’s growing clinical profile, supporting its use as an effective treatment option for adults and children with NTRK gene fusion positive tumors," said David S. Hong, M.D., Professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center. "These findings present a clear rationale for robust comprehensive genomic testing inclusive of NTRK 1/2/3 genes for patients to better understand what could be driving their cancer and appropriately match them with the right treatment approach."

"Designed specifically to treat TRK fusion cancer, Vitrakvi represents a meaningful advancement in the treatment of both adult and pediatric patients with TRK fusion cancer, inhibiting the oncogenic driver that causes these tumors to spread and grow, regardless of where they originate in the body," said Scott Z. Fields, M.D., Senior Vice President and Head of Oncology Development at Bayer. "These long-term data reinforce the use of Vitrakvi for patients with TRK fusion cancer and demonstrate our commitment to advancing the future of cancer care and providing true value for patients and physicians."

Vitrakvi adult and pediatric integrated dataset (Abstract 3108)2

An expanded dataset with longer follow-up (cut-off July 20, 2020) with 206 evaluable adult and pediatric patients with TRK fusion cancer across 21 different tumor types showed an overall response rate (ORR) per investigator assessment of 75% (95% CI 68-81), including 22% complete responses (n=45). For evaluable patients with brain metastases (n=15), the ORR was 73% (95% CI 45-92). Among all evaluable patients, the median duration of response (DoR) was 49.3 months (95% CI 27.3-NE) at a median follow-up of 22.3 months. Data on progression-free survival (PFS) and overall survival (OS) in this expanded dataset were also presented.

No new safety signals were identified. The majority of treatment-related adverse events (TRAEs) reported were primarily Grade 1 or 2, with 18% of patients reporting Grade 3 or 4 TRAEs. Two percent of patients discontinued Vitrakvi due to TRAEs and no treatment-related deaths were reported.

Data for the integrated dataset were pooled from three Vitrakvi clinical trials (NCT02122913, NCT02576431 and NCT02637687) in adult and pediatric patients with TRK fusion cancer. This analysis did not include the primary CNS patient subset.

Vitrakvi in lung cancer with or without CNS metastases (Abstract 9109)3

Updated data (cut-off July 20, 2020) on heavily pre-treated adult TRK fusion cancer patients with lung cancer, who had received a median of three prior therapies, showed Vitrakvi demonstrated consistent response rates with longer follow-up. Among 15 evaluable patients and based on investigator assessment, the confirmed ORR was 73% (95% CI 45-92), and among evaluable patients with baseline CNS metastases (n=8), the ORR was 63% (95% CI 25-91). In all evaluable patients (n=15), the 12-month rate for DoR was 81%. Data on PFS and median OS in this data subset were also presented. TRAEs were reported in 16 patients, of which two patients experienced Grade 3 events. No patients discontinued Vitrakvi due to TRAEs. These data were investigator-assessed and from patients enrolled in two clinical trials (NCT02576431, NCT02122913).

Vitrakvi in primary CNS tumors (Abstract 2002)4

In another presentation (cut-off July 20, 2020) Vitrakvi was assessed in 33 pediatric and adult patients with primary CNS tumors with an NTRK gene fusion, pooled from two clinical trials (NCT02637687, NCT02576431).The majority of patients (82%) with measurable disease experienced tumor shrinkage with an ORR of 30% (CI 95% 16-49). The 24-week disease control rate was 73% (95% CI 54-87). Data on PFS and median OS in this data subset were also presented. Grade 3 or 4 TRAEs occurred in three patients. No patients discontinued Vitrakvi due to TRAEs.

Intra-patient comparison from Vitrakvi clinical trials in TRK fusion cancer (Abstract 3114)5

Additional Vitrakvi data presented at the congress include an updated and extended retrospective growth modulation index (GMI) analysis limited to patients enrolled in Vitrakvi trials with at least one prior line of therapy. GMI is a retrospective intra-patient comparison that uses the patient as their own control by comparing PFS on current therapy to time to progression or treatment failure (TTP) on the most recent prior therapy. A GMI ratio ≥ 1.33 has been used as a threshold for meaningful clinical activity.

About Vitrakvi (larotrectinib)

Vitrakvi (larotrectinib) is indicated for the treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection will likely result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment.

Select patients for therapy based on an FDA-approved test.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information for Vitrakvi (larotrectinib)

Central Nervous System Effects: Central nervous system (CNS) adverse reactions occurred in patients receiving VITRAKVI, including dizziness, cognitive impairment, mood disorders, and sleep disturbances.

In patients who received VITRAKVI, all grades CNS effects including cognitive impairment, mood disorders, dizziness and sleep disorders were observed in 42% with Grades 3-4 in 3.9% of patients.

Cognitive impairment occurred in 11% of patients. The median time to onset of cognitive impairment was 5.6 months (range: 2 days to 41 months). Cognitive impairment occurring in ≥ 1% of patients included memory impairment (3.6%), confusional state (2.9%), disturbance in attention (2.9%), delirium (2.2%), cognitive disorders (1.4%), and Grade 3 cognitive adverse reactions occurred in 2.5% of patients. Among the 30 patients with cognitive impairment, 7% required a dose modification and 20% required dose interruption.

Mood disorders occurred in 14% of patients. The median time to onset of mood disorders was 3.9 months (range: 1 day to 40.5 months). Mood disorders occurring in ≥1% of patients included anxiety (5%), depression (3.9%), agitation (2.9%), and irritability (2.9%). Grade 3 mood disorders occurred in 0.4% of patients.

Dizziness occurred in 27% of patients, and Grade 3 dizziness occurred in 1.1% of patients. Among the 74 patients who experienced dizziness, 5% of patients required a dose modification and 5% required dose interruption.

Sleep disturbances occurred in 10% of patients. Sleep disturbances included insomnia (7%), somnolence (2.5%), and sleep disorder (0.4%). There were no Grade 3-4 sleep disturbances. Among the 28 patients who experienced sleep disturbances, 1 patient each (3.6%) required a dose modification or dose interruption.

Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed.

Skeletal Fractures: Among 187 adult patients who received VITRAKVI across clinical trials, fractures were reported in 7% and among 92 pediatric patients, fractures were reported in 9% (N=279; 8%). Median time to fracture was 11.6 months (range 0.9 to 45.8 months) in patients followed per fracture. Fractures of the femur, hip or acetabulum were reported in 4 patients (3 adult, 1 pediatric). Most fractures were associated with minimal or moderate trauma. Some fractures were associated with radiologic abnormalities suggestive of local tumor involvement. VITRAKVI treatment was interrupted due to fracture in 1.4% patients.

Promptly evaluate patients with signs or symptoms of potential fracture (e.g., pain, changes in mobility, deformity). There are no data on the effects of VITRAKVI on healing of known fractures or risk of future fractures.

Hepatotoxicity: In patients who received VITRAKVI, increased AST of any grade occurred in 52% of patients and increased ALT of any grade occurred in 45%. Grade 3-4 increased AST or ALT occurred in 3.1% and 2.5% of patients, respectively. The median time to onset of increased AST was 2.1 months (range: 1 day to 4.3 years). The median time to onset of increased ALT was 2.3 months (range: 1 day to 4.2 years). Increased AST and ALT leading to dose modifications occurred in 1.4% and 2.2% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 3 (1.1%) of patients.

Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed.

Embryo-Fetal Toxicity: VITRAKVI can cause fetal harm when administered to a pregnant woman. Larotrectinib resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the final dose of VITRAKVI.

Most Common Adverse Reactions (≥20%): The most common adverse reactions (≥20%), including laboratory abnormalities, were: increased AST (52%), increased ALT (45%), anemia (42%), musculoskeletal pain (42%), fatigue (36%), hypoalbuminemia (36%), neutropenia (36%), increased alkaline phosphatase (34%), cough (32%), leukopenia (28%), constipation (27%), diarrhea (27%), dizziness (27%), hypocalcemia (25%), nausea (25%), vomiting (25%), pyrexia (24%), lymphopenia (22%) and abdominal pain (21%).

Drug Interactions: Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors (including grapefruit or grapefruit juice), strong CYP3A4 inducers (including St. John’s wort), or sensitive CYP3A4 substrates. If coadministration of strong CYP3A4 inhibitors or inducers cannot be avoided, modify the VITRAKVI dose as recommended. If coadministration of sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs.

Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose.

Please see the full Prescribing Information for VITRAKVI (larotrectinib).

About TRK Fusion Cancer

TRK fusion cancer occurs when an NTRK gene fuses with another unrelated gene, producing a chimeric TRK protein. The altered protein, or TRK fusion protein, becomes constitutively active or overexpressed, triggering a signaling cascade. These TRK fusion proteins are oncogenic drivers promoting cell growth and survival, leading to TRK fusion cancer. TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body. TRK fusion cancer occurs in various adult and pediatric solid tumors with varying frequency, including lung, thyroid, GI cancers (colon, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS cancers (glioma and glioblastoma), salivary gland cancers (secretory carcinoma of the salivary gland) and pediatric cancers (infantile fibrosarcoma and soft tissue sarcoma).1,6

About Oncology at Bayer

Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

On May 19, 2021 Photocure ASA (OSE:PHO), the Bladder Cancer Company, reported Hexvix/Cysview revenues of NOK 81.6 million in the first quarter of 2021 (Q1 2020: NOK 54.4 million), and EBITDA of NOK 18.1 million (NOK -4.8 million), following the continued successful launch in markets previously operated by Ipsen Pharma SAS (Press release, PhotoCure, MAY 19, 2021, View Source [SID1234580326]). The third Covid-19 wave impacted operations in the quarter, but a strong March performance indicates the environment is improving.

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"For the first quarter of 2021, Photocure delivered a 50% YoY increase in Hexvix/Cysview sales, unit growth in our U.S. segment, and positive EBITDA driven by the added revenue in Europe, cost containment, and the payment from Asieris to license Hexvix in China and Taiwan. I am pleased with this performance, particularly given the negative impact from the third wave of Covid-19 in January and February of this year, foreign currency headwinds during the quarter, and the difficult comparison to the same period last year when pandemic lockdowns and limited access to care did not occur until mid-March. While access is still closed or significantly restricted in many areas, strong performance in the last month of the quarter in both our U.S. and European segments suggests that the environment is improving," says Daniel Schneider, President & Chief Executive Officer of Photocure.

Photocure reported total group revenues of NOK 88.2 million in the first quarter of 2021 (NOK 55.0 million), with an EBITDA* before restructuring of NOK 18.1 million (NOK -4.8 million) including signing fees from Asieris totaling NOK 6.4 million for the commercialization of Hexvix in Mainland China and Taiwan. Hexvix/Cysview revenues were NOK 81.6 million (NOK 54.4 million) following the successful transition of the Ipsen territories, while unit growth in the U.S. increased 4% despite the limited access to hospitals and physicians due to Covid-19. EBIT grew to NOK 12.3 million (-10.5 million) and the cash balance at the end of the first quarter 2021 was NOK 329.5 million (127.6 million).

The installed base of blue light cystoscopes in the U.S. was 280 at the end of the first quarter, an increase of 42 units, or 18%, compared to the same period in 2020. Blue Light Cystoscopy (BLC) in the surveillance setting is a key priority for Photocure in the U.S. market. By the end of the first quarter, a total base of 41 flexible cystoscopes had been installed giving more patients access to the procedure with less constraints.

"Despite the ongoing commercial challenges, we continued to advance several initiatives to grow the installed base of Blue Light Cystoscope towers and to prepare for increasing procedure volumes when full access to care reopens. In the U.S., we installed 12 new towers during the quarter including 3 flexible Blue Light Cystoscope units. Our growing pipeline suggests the potential for acceleration of Blue Light Cystoscope installations during the remainder of the year, and we believe that the benefits of Blue Light Cystoscopy with Hexvix/Cysview offering superior detection and management of bladder cancer will continue to be adopted and become the standard of care, " Schneider adds.

The ongoing Covid-19 pandemic adds continued uncertainty to Photocure’s near-term business forecast, but the Company believes that in places where procedures have been postponed due to the fear of exposure to Covid-19, the number of procedures is expected to rebound back to pre-Covid-19 growth rates in the U.S. and positive growth in the Company’s newly acquired European markets.

"Our contracting strategies in the U.S. are also gaining traction and expected to lead to new account growth and higher penetration into our existing institutional customers and physician clinics. In Europe, where we are introducing Photocure as the new sponsor of Hexvix, we have had strong buy-in from leading key opinion leaders in target countries. Despite limited access to our new customers, we are seeing early indications of a turn-around in our key growth markets such as the UK, France, and Italy. As access improves, we will continue to staff our European operations and invest in order to generate additional growth in the region. Our performance in dealing with the ongoing business volatility, including the sales rebound that we saw in March, gives me confidence that we are taking the right steps to return to strong growth and to execute on our strategy to become a leader in the diagnosis and treatment of bladder cancer patients around the world" Schneider concludes.

Please find the full financial report and presentation enclosed.

EBITDA* and other alternative performance measures (APMs) are defined and reconciled to the IFRS financial statements as a part of the APM section of the first quarter 2021 financial report on page 23.

Photocure will present its first quarter 2021 report on Wednesday 19 May 2021 at 14:00 CET. The investor presentation will be streamed live and be hosted by Daniel Schneider, CEO and Erik Dahl, CFO.

The presentation will be held in English and questions can be submitted throughout the event. The streaming event is available through https://channel.royalcast.com/landingpage/hegnarmedia/20210519_6/. The presentation is scheduled to conclude at 14:45 CET.

On May 19, 2021 Apexigen, Inc., a clinical-stage biopharmaceutical company focused on discovering and developing a new generation of antibody therapeutics for oncology, reported the presentation of clinical data from the Parker Institute for Cancer Immunotherapy’s Phase 2 clinical trial evaluating sotigalimab, Apexigen’s monoclonal antibody targeting CD40, in combination therapy for patients with metastatic pancreatic cancer at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting, being held virtually June 4-8, 2021 (Press release, Apexigen, MAY 19, 2021, View Source [SID1234590991]). Sotigalimab, Apexigen’s lead immuno-oncology therapeutic, is a potentially first-in-class and best-in-class CD40 agonist, with unique epitope specificity and Fc receptor engagement for optimal therapeutic effect and tolerability.

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"These important new data will play a critical role in our development plans for sotigalimab," said Xiaodong Yang, M.D., Ph.D., Chief Executive Officer of Apexigen. "We were thrilled to partner with the Parker Institute for Cancer Immunotherapy, Cancer Research Institute and Bristol Myers Squibb, providing our potential best-in-class CD40 therapeutic for their pancreatic cancer study to help address one of the greatest outstanding challenges in oncology. We are encouraged by the clinical benefit observed with the novel combination regimen of sotigalimab and standard of care gemcitabine/nab-paclitaxel. We believe the improvements observed in one-year overall survival, while not statistically significant as compared to the historical standard-of-care control, may provide meaningful benefit in a subset of patients with pancreatic cancer."

Dr. Yang continued, "Beyond these promising data, we are particularly encouraged by the pharmacodynamic effects of sotigalimab. These include an increase in activated myeloid dendritic cells and M1 macrophages, which demonstrates the on-mechanism and differentiated activity of sotigalimab. In addition, the identification of a unique biomarker signature that was associated with clinical benefit of treatment with sotigalimab plus chemotherapy may play a critical role in guiding our clinical strategy, as well as enabling the identification and selection of patients most likely to benefit from sotigalimab. Based on these clinical and biomarker data, we expect an additional Phase 2 trial with more patients and a biomarker-based patient selection strategy may be needed before launching a Phase 3 trial in this indication. We look forward to leveraging these important learnings in our ongoing and future studies, building upon our foundation of compelling single-agent activity in immunotherapy-naïve melanoma, durable activity in PD-1 refractory melanoma, and promising activity in our target combinations of chemotherapy and/or radiation in other solid tumors. To maximize the full therapeutic potential of sotigalimab, we have implemented a broad and comprehensive clinical development strategy and are currently conducting several Phase 2 trials across indications, lines of therapies and combination settings, from which we anticipate multiple milestones and near-term data readouts."

The poster titled, "Gemcitabine and nab-Paclitaxel ± Nivolumab ± CD40 Agonistic Monoclonal Antibody Sotigalimab (APX005M) in Participants with Untreated Metastatic Pancreatic Adenocarcinoma: Phase 2 Final Results", will be presented by Mark O’Hara, M.D., an assistant professor of Medicine, in the division of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania (Abstract #4019; Track: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary). The poster has been selected for presentation as part of a Poster Discussion Session from 9:00-10:00 a.m. ET on Friday, June 4, 2021. The poster will also be available on-demand through the ASCO (Free ASCO Whitepaper) conference portal, starting at 9:00 a.m. ET.

Summary of the data:
The Phase 2 study evaluated multiple novel combination regimens on top of standard of care gemcitabine/nab-paclitaxel (Gem+NP) in three cohorts: Cohort A1 (Gem+NP+Nivolumab), Cohort B2 (Gem+NP+Sotigalimab 0.3 mg/kg), and cohort C2 (Gem+NP+Nivolumbab+Sotigalimab 0.3 mg/kg). Each cohort was designed to be compared against a historical control OS.
The primary endpoint was 1-year overall survival (OS) as compared to the historical control standard of care (Gem+NP) of 35%. The one-year OS was 57.3% for A1 (P=0.007, n=34), 48.1% for B2 (P=0.062, n=36), and 41.3% for C2 (P=0.236, n=35). Improvements in OS were statistically significant for cohort A1, with moderate clinical activity observed in cohort B2
Safety profiles across all three cohorts were manageable and consistent with previously reported Phase 1b data, suggesting sotigalimab may be well tolerated when utilized in multiple combination therapy strategies
An increase of activated myeloid dendritic cells (CD86+ mDC) was found in the patients treated with sotigalimab containing regimens (Cohorts B2 and C2)
An increase of tumoral M1 macrophages was found only in patients treated with sotigalimab+chemotherapy (Cohort B2)
Lower baseline levels of effector memory CD8+ T cells, exhausted effector memory CD4+ T cells and TNF and MYC gene expression were associated with improved survival with sotigalimab+chemotherapy (Cohort B2)
Additional biomarker results from the Phase 2 study will be presented in a poster titled, "Baseline level and early on-treatment clearance of circulating mutant KRAS in metastatic pancreatic ductal adenocarcinoma treated with chemotherapy with or without immunotherapy", to be presented by Jacob Till, M.D., Ph.D., Senior Research Investigator, at Penn. (Abstract #4122; Track: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary).

About the Phase 1b/2 Clinical Trial
In the Phase 1b portion of this open-label, multicenter Phase 1b/2 clinical trial, previously untreated patients with metastatic pancreatic ductal adenocarcinoma received sotigalimab in combination with gemcitabine and nab-paclitaxel, a standard-of-care chemotherapy regimen for this patient population, and half of the patients also received Bristol Myers Squibb’s PD-1 inhibitor, nivolumab. The Phase 2 portion of the trial evaluated multiple combination regimens on top of standard of care gemcitabine/nab-paclitaxel (Gem+NP): Gem+NP plus sotigalimab, Gem+NP plus nivolumab and Gem+NP plus sotigalimab and nivolumab. The primary endpoint was 1-year overall survival (OS) rate compared with a 35% historical rate for Gem+NP. Secondary endpoint results included safety (adverse events [AEs], treatment-related adverse events [TRAEs]), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and duration of response (DOR). Exploratory endpoints included immune pharmacodynamics, associations between tumor and immune biomarkers and clinical outcomes, and baseline and on-treatment microbiome profiles. For additional information on this trial (NCT03214250), please visit www.clinicaltrials.gov.

About Sotigalimab (APX005M)
Sotigalimab is a novel, humanized monoclonal antibody that stimulates the anti-tumor immune response. Sotigalimab targets CD40, a co-stimulatory receptor that is essential for activating both innate and adaptive immune systems. Binding of Sotigalimab to CD40 on antigen presenting cells (i.e., dendritic cells, monocytes and B-cells) initiates a multi-faceted immune response bringing multiple components of the immune system (e.g., T cells, macrophages) to work in concert against cancer. Sotigalimab is currently in Phase 2 clinical development for the treatment of cancers such as pancreatic cancer, esophageal and gastroesophageal junction cancers, melanoma, non-small cell lung cancer, rectal cancer and sarcoma in various combinations with immunotherapy, chemotherapy, radiation therapy or a cancer vaccine. Additional information on clinical trials for Sotigalimab can be found at www.clinicaltrials.gov.

On May 19, 2021 xCures reported their collaboration with the FibroFighters Foundation to launch a real-time learning platform for the Fibrolamellar Hepatocellular Carcinoma (FLHCC) community (Press release, xCures, MAY 19, 2021, View Source [SID1234584919]). FLHCC is a rare cancer primarily affecting adolescents and young adults. With an annual incidence of fewer than 300 cases, little is known regarding the best treatment options.

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The xCures platform is a direct-to-patient research program that brings together patients, clinicians, patient advocates, and researchers, to accelerate the understanding of cancers and find better treatments faster.

Tom Stockwell, Executive Director of FibroFighters commented "We are very excited to be working with xCures on this important project". "This platform will have an immediate impact across many of our patients’ lives." He added, "I only wish this extremely valuable tool could have been available during my son’s fight." Tom has dedicated his life to helping FLHCC patients and families.

"xCures, FibroFighters, and the entire Fibrolamellar patient community are working together to advance knowledge about FLHCC across the country and around the world," stated Mika Newton, xCures’ CEO. "This partnership will leverage access to leading therapeutics, diagnostics, and algorithms to improve patient outcomes at the point of care and provide much needed real-time data for doctors treating this rare cancer."

For FLHCC patients, xCures integrates medical records into a clear patient summary report suitable for sharing with their oncologist, including their case summary, a list of top options, the rationale supporting each recommendation, and how to access the options.

Treatment options are informed by real-world data collected on the xCures platform, learning from the experiences of all FLHCC patients, and using AI algorithms to better understand which treatments work better for different FLHCC patients and why. Novel options and therapeutic rationales are sourced from expert oncologists and key opinion leaders in treatment of FLHCC.

xCures also helps patients access treatment options through trial matching, managed access, compassionate use programs, and by supporting insurance coverage of treatments with data. At the patient’s request, xCures may also convene a Virtual Tumor Board (VTB) where nationally recognized cancer experts further refine the xCures options summary based on a discussion of the patient’s personal medical history and preferences.

xCures and FibroFighters are actively assembling this expert panel for the Fibrolamellar community.