On February 16, 2023 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, reported financial results for the fourth quarter ended December 31, 2022, and provided a business update (Press release, BerGenBio, FEB 16, 2023, View Source [SID1234627294]).

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A briefing by BerGenBio’s senior management team will take place at 10:00 am CET today via a webcast presentation, followed by a Q&A session. Please see below for details.

"The recent announcement of the topline data from our BCBG008 NSCLC trial corroborates the strategy we enacted and the great strides we took in 2022," said Martin Olin, Chief Executive Officer of BerGenBio. "The trial showed a survival benefit and disease control provided by bemcentinib in combination with pembrolizumab, substantiating the relevance of AXL inhibition in NSCLC, particularly in patients with AXL-expressing tumors. The results of the trial strongly support our efforts to treat 1L NSCLC patients harboring STK11 mutations, a group in which AXL expression commonly occurs. Bemcentinib’s ability to selectively inhibit AXL may serve as a key component in delivering hope to this large, hard-to-treat patient population."

Clinical Development

Bemcentinib

BerGenBio’s lead compound, bemcentinib, is a potentially first-in-class, oral, highly selective inhibitor of the receptor tyrosine kinase AXL, which is expressed and activated in response to oxidative stress, inflammation, hypoxia, and drug treatment, resulting in a number of deleterious effects in cancer and severe respiratory infections. Bemcentinib selectively inhibits AXL activation to prevent the progression of serious diseases through the modulation of resistance mechanisms and the adaptive immune system.

Bemcentinib is currently being developed in STK11 mutated NSCLC and severe respiratory infections including COVID-19. Its novel mechanisms of action and primary accumulation in the lungs uniquely position it to address these severe lung diseases.

Oncology: NSCLC

2L+ NSCLC Trial (BGBC008)

Subsequent to quarter end, the Company announced topline data from the BGBC008 (2L+) NSCLC trial on February 15, 2023. The trial enrolled 90 evaluable patients who received at least one prior line of therapy: chemotherapy, immunotherapy or the combination. Topline results from the total evaluable population:

A clinically meaningful survival benefit and evidence of disease control was demonstrated with bemcentinibin combination with pembrolizumab regardless of prior therapy, providing a median overall survival (mOS) of 13.0 months (95% CI: 10.1, 16.7), median progression free survival (mPFS) of 6.2 months (95% CI: 4.6, 9.8), disease control rate (DCR) of 51.1% (95% CI: 40.3, 61.8) and overall response rate (ORR) of 11.1% (95% CI: 6.2, 18.1).
A significant (p-value < 0.05) and clinically meaningful improvement in mOS based on AXL tumor proportion score (TPS) was observed. Patients with AXL TPS > 5 (46% of evaluable patients) achieved a mOS of 14.8 months (95% CI: 12.4, 29.6) compared to patients with AXL TPS < 5, who achieved a mOS of 9.9 months (95% CI: 6.7, 17.4). In addition, patients with an AXL TPS > 5 had a mPFS of 8.7 months (95% CI: 6.0, 14.8) compared to 4.6 months (95% CI: 2.7, 8.1) for patients with AXL TPS < 5. The ORR for AXL TPS > 5 was 21.9%.
The observed mOS was similar regardless of patient PD-L1 status.
Treatment with bemcentinib in combination with pembrolizumab was well-tolerated.
2L+ NSCLC Trial (BGBIL005)

In addition to the encouraging ORR and DCR data previously presented from the Investigator Led Study phase 1 trial in which bemcentinib was combined with docetaxel, the final mPFS of 3.1 months and mOS of 12.3 months support the clinical benefit of combining bemcentinib with chemotherapy.

1L STK11m NSCLC (BGBC016)

BerGenBio announced in October 2022 the initiation of a global, open label phase 1b/2a trial evaluating bemcentinib in combination with the current standard of care, pembrolizumab and platinum doublet chemotherapy, for the treatment of 1L NSCLC patients harboring STK11 mutations. The trial is designed to determine the safety, tolerability, and efficacy of bemcentinib with standard of care in 1L advanced/metastatic non-squamous NSCLC patients with STK11 mutations and no other actionable co-mutations.

A significant subgroup comprising approximately 20% (> 30,000 patients in US and EU5) of non-squamous NSCLC patients harbor STK11 mutations, which are associated with immunosuppression and poor prognosis with standard treatment in 1L NSCLC. Data suggests that STK11m NSCLC patients almost universally have AXL tumor expression and activation, resulting in the development of drug resistance, immune evasion, and metastases.

Topline data from the 2L+ NSCLC (BGBC008) trial show clinically meaningful mOS, mPFS and DCR with the combination of bemcentinib and pembrolizumab, regardless of prior therapy. In patients with an AXL TPS > 5, a clinically significant improvement in mOS was observed providing supporting evidence for the relevance of AXL inhibition in the treatment of NSCLC. Further, data from the 2L+ NSCLC (BGBIL005) trial indicated promising clinical benefits from administering bemcentinib with chemotherapy.

The results of the BCBG008 and BCBIL005 trials provide clinical evidence of the anti-tumor effects of bemcentinib and its ability to modulate the tumor microenvironment to enhance the effects of immunotherapy and chemotherapy and provide strong support for the ongoing 1L NSCLC trial in patients harboring STK11 mutations, that are characterized by a severely immunosuppressed, pro-tumorigenic microenvironment and AXL activation.

Screening of patients for the 1L STK11m NSCLC (BCBG016) trial is ongoing.

Oncology: Relapsed/Refractory AML

As previously announced, the Company expects to report topline results from the phase 2 BGBC003 trial in Relapsed/Refractory AML in H1 2023.

Severe Respiratory Infections (SRIs)

The Company believes that bemcentinib blocks viral entry and replication, stimulates the innate immune system, and promotes lung tissue repair positioning it for the treatment of severe respiratory infections including COVID-19.

Previously the Company has completed two phase 2 trials with bemcentinib in hospitalized COVID-19 patients, showing promising clinical activity and is currently enrolling patients into the EUSolidAct phase 2b platform trial in hospitalized COVID-19 patients.

The trial is sponsored, and majority funded by the EUSolidAct platform, a pan-European research project designed to investigate treatment options for hospitalized patients with COVID-19 and emerging infectious diseases. The sponsor and the Company are currently monitoring the evolution of the pandemic and its impact on the trial execution. Further guidance on the trial is expected in H1 2023.

Additionally, bemcentinib is being evaluated in preclinical studies for SRIs causing Acute Respiratory Distress Syndrome (ARDS) and initial results are expected during 2023.

Corporate Activities

Shareholder Loan Facility

BerGenBio announced in October that it secured a shareholder loan facility of up to NOK 100 million from Meteva AS, a 27.23% shareholder in BerGenBio. The Company can draw on the facility from Q2 2023. In addition to the Company’s existing cash position, the facility will enable BerGenBio to continue advancing its lead compound, bemcentinib, in 1L STK11m NSCLC and hospitalized COVID-19 patients.

Oncology Scientific Advisory Board

Subsequent to the quarter end, BerGenBio announced in February the formation of a scientific advisory board to enhance the development of bemcentinib for the treatment of NSCLC patients with STK11m, consisting of four world-renowned non-small cell lung cancer experts from top oncology centers around the globe: Enriqueta Felip, M.D., Ph.D., Head of the Thoracic Cancer Unit at Vall d’Hebron University Hospital, Spain; John Heymach, M.D., Ph.D., Chair of Thoracic/Head and Neck Medical Oncology at the MD Anderson Cancer Center, Texas; Tony Mok, M.D., BMSc., Professor and Chairman of the Department of Clinical Oncology at the Chinese University of Hong Kong; and Solange Peters, M.D., Ph.D., Professor and Head of Medical Oncology and Thoracic Malignancies at the Department of Oncology at Lausanne University, Switzerland.

Fourth Quarter 2022 and Full Year Financial Highlights

(Figures in brackets = same period 2021 unless otherwise stated)

Revenue amounted to NOK 0.4 million (NOK 0.8 million) for the fourth quarter and NOK 0.4 million (NOK 0.8 million) for the full year 2022
Total operating expenses for the fourth quarter were NOK 76.8 million (NOK 68.1 million) and total operating expenses for the full year 2022 amounted to 306.0 million (NOK 315.2 million)
The operating loss for the quarter came to NOK 76.4 million (NOK 67.3 million) and NOK 305.6 million (NOK 314.5 million) for the full year 2022
Cash and cash equivalents amounted to NOK 150.8 million at the end of December 2022 (NOK 436.6 million by end of December 2021). The cash position in addition to the shareholder loan facility secured from Meteva AS of up to NOK 100 million is estimated to fund planned activities through 2023 on a going concern basis.
Webcast Details

The live webcast link is available at www.bergenbio.com in the Investors/Financial Reports section. A recording will be available shortly after the webcast has finished.

Webcast link: https://channel.royalcast.com/landingpage/hegnarmedia/20230216_14/

Dial-in numbers:

NO: +47-21-956342

UK: +44-203-7696819

US: +1 646-787-0157

SE: +46-4-0682-0620

DK: +45 78768490

Pin: 712491

The fourth quarter and full year report and presentation are available on the Company’s website in the Investors/Financial Reports section.

On February 16, 2023 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers, reported its early Phase 1 results for BPX-601 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) in San Francisco and virtually (Press release, Bellicum Pharmaceuticals, FEB 16, 2023, View Source [SID1234627293]). The poster titled "Early Results from a Phase 1, Multicenter Trial of PSCA-Specific GoCAR T Cells (BPX-601) in Patients with Metastatic Castration-Resistant Prostate Cancer (mCRPC)" presents initial data from the first two cohorts (n=8) treated with BPX-601. These interim results demonstrated preliminary efficacy of BPX-601 PSCA-directed GoCAR-T cells in combination with rimiducid in heavily pre-treated patients.

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"We believe these encouraging initial clinical results in mCRPC support the potential of BPX-601 and the GoCAR-T platform," stated Rick Fair, President and Chief Executive Officer, Bellicum Pharmaceuticals. "We designed the GoCAR-T platform to enhance immune cell proliferation and persistence, resist exhaustion, and override key inhibitory factors in the solid tumor microenvironment. We are excited to share data supporting the clinical activity of the first GoCAR-T program early in dose escalation, and look forward to reporting additional results as we work to optimize the doses of BPX-601 cells and rimiducid."

Initial Results from Ongoing BPX-601 Phase 1 Trial

These initial data from 2 cohorts consisted of 8 patients who received lympodepleting chemotherapy (fludarabine + cyclophosphamide) followed by a single dose of 5×106 BPX-601 cells/kg and single (n=3) or weekly (n=5) doses of 0.4 mg/kg rimiducid beginning 7 days following the cell infusion. GoCAR-T cells are designed to function optimally with repeat dosing of rimiducid to induce the co-activation molecules MyD88 and CD40. The primary observations were:

Four of eight (50%) patients achieved a PSA50 response, three of whom achieved a PSA90 response.
Of the six patients with soft tissue (visceral and/or lymph node) disease, two achieved partial responses by RECIST v1.1, one of which was confirmed.
Of the two patients with bone-only disease, one patient achieved a PSA90 response with decreased enhancement of bone lesions observed on bone scan.
The most common grade 3+ adverse events were myelosuppression, characteristic of the lymphodepleting chemotherapies used in CAR-T studies. Two patients experienced Grade 3 cytokine release syndrome (CRS). One patient experienced Grade 4 immune effector cell neurotoxicity syndrome (ICANS) with concurrent hemophagocytic lymphohistiocytosis (HLH); while ICANS improved to grade 1 with standard of care treatment and withholding of subsequent doses of rimiducid, the patient died on study day 20 due to sepsis. Interpretation of immune-mediated adverse events in this patient is confounded by concurrent sepsis.
Consistent BPX-601 cell expansion across patients was observed, with persistence of BPX-601 cells detected in peripheral blood over 200 days.
Evidence of inducible MyD88/CD40 (iMC) activation was observed, with serum levels of pro-inflammatory T cell cytokines (including IFNγ, TNFα, IL-6 and IP-10) rising after administration of rimiducid and subsequently falling prior to subsequent doses.
BPX-601 cell infiltration in PSCA-positive tumor was observed.
The trial continues to enroll patients. The next cohorts in the Phase 1 trial will explore higher doses of rimiducid, which in non-clinical studies have been shown to increase GoCAR-T persistence, enhance pro-inflammatory cytokine production, and improve anti-tumor efficacy.

About BPX-601

BPX-601, the company’s first GoCAR-T product candidate, incorporates iMC, Bellicum’s inducible co-activation domain. iMC (inducible MyD88/CD40) is designed to provide a powerful boost to T cell proliferation and persistence, production of immunomodulatory cytokines and enable the CAR-T to override key immune inhibitory mechanisms, including PD-1 and TGF-beta. BPX-601 is being evaluated as a treatment for metastatic castration resistant prostate cancer (mCRPC) expressing prostate stem cell antigen (PSCA).

On February 16, 2023 Aura Biosciences, Inc. ("Aura") (Nasdaq: AURA), a clinical-stage biotechnology company developing a novel class of virus-like drug conjugate (VDC) therapies for multiple oncology indications, reported the presentation of positive interim Phase 2 safety and efficacy data of bel-sar with 9-10 months of follow up evaluating two key clinical endpoints: tumor control and visual acuity preservation using the suprachoroidal (SC) route of administration for the first-line treatment of patients with early-stage choroidal melanoma (indeterminate lesions and small choroidal melanoma (IL/CM)) (Press release, Aura Biosciences, FEB 16, 2023, View Source [SID1234627292]). The results were presented at the Macula Society 46th Annual Meeting held February 15-18, 2023, in Miami, FL.

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"The data presented today with an average of nine months of follow up for patients treated with three cycles of therapy, show an excellent response to the therapy with 89-100% tumor control. In addition, the safety profile to date has been favorable with only one patient losing visual acuity and no treatment-related SAEs or significant AEs, which is encouraging given that the majority of these patients had tumors close to the fovea or optic disk and would have likely experienced severe and irreversible vision loss with the current standard of care with radiotherapy," said Dr. Ivana Kim, Director of the Ocular Melanoma Center, Massachusetts Eye and Ear. "These latest results strongly support the potential of bel-sar to be used as a first line treatment option for patients with early-stage choroidal melanoma."

"We are excited with the interim efficacy data of the Phase 2 study which strongly supports the assumptions for the success of the global Phase 3 trial," said Dr. Cadmus Rich, Chief Medical Officer of Aura Biosciences. "Collectively, we believe these interim data provide strong confidence to support the launch of a global Phase 3 trial which is on track to begin enrollment this year."

The presentation can be accessed on the Company’s website: link

Updated Safety and Efficacy Data from the Ongoing Phase 2 Trial with SC Administration

This Phase 2 trial (NCT04417530) is assessing the safety and preliminary efficacy of single- and multiple ascending-doses of bel-sar up to three cycles of treatment via SC administration for the first-line treatment of early-stage choroidal melanoma. A total of 20 adult patients have been enrolled in the trial including the single dose Cohorts 1-3 (n=6) and multiple dose escalation Cohorts 4-6 (n=14). Cohorts 5 and 6 received up to three cycles of therapy, which was considered the therapeutic regimen for evaluation. One patient in Cohort 5 (n=3) received two cycles of therapy and two patients in Cohort 5 received three cycles of therapy (40 µg/dose). All patients from Cohort 6 (n=8) were assigned to receive three cycles of therapy at the highest dose (80 µg/dose). One patient from Cohort 6, who discontinued after one cycle due to unrelated serious adverse events (SAEs), is not included. All patients in Cohorts 5 and 6 had active growth at study entry, as an enrichment strategy to evaluate preliminary efficacy. This group of patients with active growth treated at the therapeutic regimen of three cycles was evaluated for tumor growth rate, tumor control, and visual acuity preservation as the defined clinical endpoints to evaluate preliminary efficacy. The results, with an average of nine months of follow up in patients who received three cycles of therapy in Cohorts 5 and 6, and who match the criteria for the planned global Phase 3 trial, showed a

statistically significant reduction in the tumor growth rate (-0.289 mm/yr, p = <0.0001) compared to each patient’s documented growth rate at study entry, and a 100% (8/8) tumor control rate. In addition, the visual acuity preservation rate was 88% (7/8) in these cohorts, with the majority of patients being at high-risk for vision loss with tumors close to fovea or optic disk. The overall tolerability profile of bel-sar was generally favorable, with no dose-limiting toxicities, treatment-related SAEs or significant AEs reported as of January 10, 2023. There was no posterior inflammation and only mild anterior inflammation (Grade 1) in 20% of the patients. Treatment-related AEs were predominantly mild and resolved without sequalae. We believe these interim results indicate that bel-sar may offer a targeted, vision preserving therapy for the first-line treatment of primary CM, where 80% of patients are diagnosed early and have no approved therapies to date.

On February 16, 2023 Arbutus Biopharma Corporation (Nasdaq: ABUS), a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to develop novel therapeutics that target specific viral diseases, reported that it has scheduled its fourth quarter and year end 2022 financial results and corporate update for Thursday, March 2, 2023 (Press release, Arbutus Biopharma, FEB 16, 2023, View Source [SID1234627291]). The schedule for the press release and conference call/webcast are as follows:

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• Q4 and Year End 2022 Press Release: Thursday, March 2, 2023 at 7:30 a.m. ET
• Q4 and Year End 2022 Conference Call/Webcast: Thursday, March 2, 2023 at 8:45 a.m. ET

To dial-in for the conference call by phone, please register using the following link: Registration Link. A live webcast of the conference call can be accessed through the Investors section of Arbutus’ website at www.arbutusbio.com.

An archived webcast will be available on the Arbutus website after the event.

On February 16, 2023 ALX Oncology Holdings Inc., ("ALX Oncology") (Nasdaq: ALXO), a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint pathway, reported the first patient has been dosed in the ASPEN-07 study evaluating evorpacept, a next generation CD47 blocker, in combination with PADCEV (enfortumab vedotin-ejfv), an antibody drug conjugate ("ADC"), in patients with urothelial cancer ("UC") (Press release, ALX Oncology, FEB 16, 2023, View Source [SID1234627290]).

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ASPEN-07 is a phase 1, open-label, multi-center study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of evorpacept in combination with enfortumab vedotin-ejfv in subjects with unresectable locally advanced or metastatic UC (NCT05524545).

"Outcomes for patients diagnosed with locally advanced or metastatic UC remain poor, and treatment options after initial chemotherapy and immunotherapy are limited," said Sophia Randolph, M.D., Ph.D., ALX Oncology’s Chief Medical Officer. "We are excited to initiate ASPEN-07 to investigate this novel combination therapy that has the potential to change the treatment course of advanced UC. We are encouraged that PADCEV is the first ADC therapy to demonstrate meaningful clinical activity in these difficult-to-treat patients, and the addition of a CD47 blocker is expected to act through different but complementary mechanisms to positively impact efficacy without increasing toxicity."

About Bladder and Urothelial Cancer
As estimated by the National Cancer Institute, bladder cancer is the sixth most common cancer type in the United States. Urothelial cancer is the most common type of bladder cancer and accounts for approximately 90% of all bladder cancer cases. 81,000 new cases of bladder cancer will be diagnosed in the United States in 2022 with over 17,000 deaths. The five-year survival for patients with metastatic bladder cancer is less than 8%. Worldwide, over 573,000 new cases of bladder cancer and over 212,000 deaths occurred in 2020 according to The Global Cancer Observatory