On August 4, 2022 bluebird bio, Inc. (NASDAQ: BLUE) ("bluebird bio" or the "Company") reported financial results and business highlights for the second quarter ended June 30, 2022, and shared recent operational progress (Press release, bluebird bio, AUG 4, 2022, View Source [SID1234617542]).

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"The second quarter marked significant progress for bluebird bio and a precedent-setting moment for the field of gene therapy," said Andrew Obenshain, chief executive officer, bluebird bio. "With the FDA advisory committee’s unanimous support for beti-cel and eli-cel for their target indications, we are now laser-focused on commercial readiness, and if approved, we anticipate launching both therapies in the fourth quarter of this year. Additionally, this quarter we advanced the remaining CMC steps ahead of our lovo-cel BLA submission, and we remain on track to submit the BLA in the first quarter of next year."

RECENT HIGHLIGHTS

BETI-CEL

UNANIMOUS POSITIVE VOTE AT FDA ADVISORY COMMITTEE MEETING – On June 10, the U.S. Food and Drug Administration’s (FDA) Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) voted (13-0) that the benefits of betibeglogene autotemcel (beti-cel) gene therapy outweigh the risks for people with beta-thalassemia who require regular red blood cell transfusions. If approved, beti-cel will be the first ex-vivo LVV gene therapy available in the U.S.
ICER REVIEW – The Institute for Clinical and Economic Review (ICER) completed its review of beti-cel for people with beta-thalassemia and determined in its final report that beti-cel will be cost effective at a price up to $3.0 million. bluebird anticipates setting a price for beti-cel upon potential FDA approval.
ELI-CEL

UNANIMOUS POSITIVE VOTE AT FDA ADVISORY COMMITTEE MEETING – On June 9, the FDA CTGTAC voted (15-0) that the benefits of elivaldogene autotemcel (eli-cel) gene therapy outweigh the risks for the treatment of any sub-population of children with early active cerebral adrenoleukodystrophy (CALD). If approved, eli-cel will be the first and only gene therapy for the treatment of early active CALD, a rare neurodegenerative disease that primarily affects young children and leads to irreversible loss of neurologic function and death.
LOVO-CEL

CONTINUED PROGRESS TOWARD BLA SUBMISSION – bluebird bio remains on track to submit a biologics licensing application (BLA) to the FDA for lovotibeglogene autotemcel (lovo-cel) for sickle cell disease in the first quarter of 2023. As previously communicated, the Company has treated all patients in HGB-206 Group C who will form the primary basis of efficacy for BLA submission. This quarter, the Company completed manufacturing of commercial drug product validation lots, marking significant progress on CMC requirements and final steps to BLA submission. Additionally, bluebird completed enrollment of all patients in the HGB-210 study necessary to support manufacturing data requirements for the BLA submission. The remaining step prior to BLA submission is completion of vector and drug product analytical comparability, which the Company expects to complete in the fourth quarter of 2022.

The Company remains in active dialogue with the FDA about the resolution of the partial clinical hold for patients under 18. The Company is continuing to enroll and treat patients 18 and older in the HGB-210 study.
COMPANY

TOM KLIMA APPOINTED CHIEF COMMERCIAL & OPERATING OFFICER – Effective August 8, Tom Klima will serve as Chief Commercial & Operating Officer. Klima joined bluebird in May 2021 as Chief Commercial Officer to hone the Company’s commercial strategy and oversee launch execution plans for its gene therapy portfolio. His new role reflects expanded responsibilities for program management and patient supply chain in addition to sales, marketing and market access.
UPCOMING INVESTOR EVENT

Members of the management team will participate in the 2022 Wedbush PacGrow Virtual Healthcare Conference, Wednesday, August 10, at 9:10 a.m. ET as part of the panel titled Miss Con-GENE-iality – Updates in Gene Tx.

UPCOMING ANTICIPATED MILESTONES

BETI-CEL

The FDA has set a PDUFA goal date for August 19, 2022, and if approved, the Company anticipates first apheresis in the fourth quarter of 2022.
beti-cel is being reviewed under Priority Review for the treatment of beta-thalassemia in patients requiring regular red blood cell transfusions. bluebird bio anticipates receiving a Priority Review Voucher (PRV) upon potential approval of beti-cel.
ELI-CEL

The FDA has set a PDUFA goal date of September 16, 2022, and if approved, the Company anticipates therapy availability in the fourth quarter of 2022.
eli-cel is being reviewed under Priority Review for the treatment of cerebral adrenoleukodytrophy in patients less than 18 years of age who do not have an available and willing human leukocyte antigen (HLA)-matched sibling hematopoietic stem cell (HSC) donor. bluebird bio anticipates receiving a PRV upon potential approval of eli-cel.
bluebird bio is in active communication with the FDA to resolve the eli-cel clinical hold and anticipates the FDA’s questions may be resolved concurrent with the agency’s ongoing review of the Company’s BLA submission.
LOVO-CEL

The Company is in active communication with the FDA to resolve the lovo-cel partial clinical hold and resume enrollment and treatment of patients under the age of 18.
The Company expects to complete vector and drug product analytical comparability in the fourth quarter of 2022.
The Company plans to submit its BLA for lovo-cel in Q1 2023.
SECOND QUARTER 2022 FINANCIAL RESULTS

Cash Position: The Company’s restricted cash, cash and cash equivalents and marketable securities balance was approximately $218 million, including restricted cash of approximately $45 million, as of June 30, 2022. The full-year 2022 cash burn is expected to be less than $340 million.

As of today, the Company has raised approximately $24.7 million in gross proceeds through its At-the-Market (ATM) equity facility. Of this $24.7 million, $8.0 million in net proceeds were realized in the second quarter and are reflected in the restricted cash, cash and cash equivalents and marketable securities balanced as of June 30, 2022. The Company is exploring additional financing opportunities, including public or private equity financings and monetizing any priority review vouchers that may be issued upon approval of beti-cel or eli-cel.
Revenues: Total revenue was $1.5 million for the three months ended June 30, 2022, compared to $0.1 million for the three months ended June 30, 2021.
R&D Expenses: Research and development expenses from continuing operations were $63.8 million for the three months ended June 30, 2022, compared to $84.6 million for the three months ended June 30, 2021. The decrease of $20.8 million was primarily due to decreased employee compensation, benefits, other head-count related expenses, information technology and facility-related costs, lab expenses and clinical trial costs. These decreased costs were partially offset by increased manufacturing costs.
SG&A Expenses: Selling, general and administrative expenses from continuing operations were $36.7 million for the three months ended June 30, 2022, compared to $55.0 million for the three months ended June 30, 2021. The decrease of $18.3 million was primarily due to decreased employee compensation, benefit, and other head-count related expenses and decreased commercial readiness activities due to the Company’s decision to focus its efforts on the U.S. market for beti-cel, eli-cel, and lovo-cel. These decreased costs were partially offset by increased information technology and facility-related costs due to the addition of the Company’s office lease in Somerville, Massachusetts.
Net Loss: Net loss from continuing operations was $100.1 million for the three months ended June 30, 2022, compared to $155.8 million for the three months ended June 30, 2021.

On August 4, 2022 DURECT Corporation (Nasdaq: DRRX) reported financial results for the three months ended June 30, 2022 and provided a corporate update (Press release, DURECT, AUG 4, 2022, View Source [SID1234617558]).

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"We continue to see enrollment accelerating in the larsucosterol (DUR-928) AHFIRM trial and are pleased to announce that we have enrolled 170 patients to date. The second quarter continued the recent positive enrollment trend, with more patients dosed than in any prior quarter, reflecting the opening of additional clinical trial sites and our ongoing efforts to work with existing sites to recruit more patients with severe alcohol-associated hepatitis (AH) that meet our enrollment criteria," stated James E. Brown, D.V.M., President and CEO of DURECT.

Second Quarter and Recent Business Highlights:

Continued progress in AHFIRM enrollment – DURECT has enrolled 170 patients in the AHFIRM trial to date, which exceeds 50% of the target enrollment for the 300-patient trial. We now have over 60 AHFIRM study sites open at leading hospitals in the U.S., Australia, E.U. and U.K. We continue to expect to enroll the last patient in the AHFIRM trial in mid-2023, which should enable top-line results to be reported in the second half of 2023.
FDA agreement on modified primary endpoint to include liver transplant in addition to mortality – Through a Type C meeting with the U.S. Food and Drug Administration (FDA), FDA has concurred with DURECT’s proposal to amend the primary endpoint of the ongoing AHFIRM trial to be the reduction in mortality or liver transplant at 90 days. A liver transplant represents a serious and expensive medical event for patients and we believe that including transplanted patients as well as mortality in the primary endpoint better reflects the current state of care for AH patients.
Recent Patent Issuance covering POSIMIR – On August 2, 2022, DURECT was issued a new patent by the US Patent Office, extending US patent coverage for POSIMIR to at least 2041. This event triggered an $8 million milestone payment due to DURECT under our license agreement with Innocoll Pharmaceuticals Limited (Innocoll). This payment is in addition to the $4 million upfront license fee received in January 2022, and a $2 million milestone payment to be received upon the first commercial sale of POSIMIR in the United States.
Financial Highlights for Q2 2022:

Total revenues were $2.1 million and net loss was $11.6 million for the three months ended June 30, 2022 compared to total revenues of $2.3 million and net loss of $9.1 million for the three months ended June 30, 2021.
At June 30, 2022, cash and investments were $54.3 million, compared to cash and investments of $70.0 million at December 31, 2021. Total debt at June 30, 2022 was $20.9 million, compared to $20.6 million at December 31, 2021.
Earnings Conference Ca ll
We will host a conference call today at 4:30 p.m. Eastern Time/1:30 p.m. Pacific Time to discuss second quarter 2022 results and provide a corporate update:

A live audio webcast of the presentation will be also available by accessing DURECT’s homepage at www.durect.com and clicking "Investors." If you are unable to participate during the live webcast, the call will be archived on DURECT’s website under "Event Calendar" in the "Investors" section.

About the AHFIRM Trial
Enrollment is ongoing in our Phase 2b randomized, double-blind, placebo-controlled, international, multi-center study in subjects with severe acute alcohol-associated hepatitis (AH) to evaluate saFety and effIcacy of laRsucosterol (DUR-928) treatMent (AHFIRM). The study is comprised of three arms targeting enrollment of 300 total patients, with approximately 100 patients in each arm: (1) Placebo plus supportive care, with or without methylprednisolone capsules at the investigators’ discretion; (2) larsucosterol (30 mg); and (3) larsucosterol (90 mg). Patients in the larsucosterol arms receive the same supportive care without steroids. In order to maintain blinding, patients in the two active arms receive matching placebo capsules if the investigator prescribes steroids. The primary outcome measure will be the 90-Day incidence of mortality or liver transplantation for patients treated with larsucosterol compared to those treated with placebo. The Company is enrolling patients at more than 60 clinical trial sites across the U.S., EU, U.K., and Australia. Reflecting the life-threatening nature of AH and the lack of therapeutic options, the U.S. Food and Drug Administration (FDA) has granted larsucosterol Fast Track Designation for the treatment of AH. We believe a positive outcome in the AHFIRM trial could support a New Drug Application filing. For more information, refer to ClinicalTrials.gov Identifier: NCT04563026.

About Alcohol-associated Hepatitis (AH)
AH is a life-threatening acute alcohol-associated liver disease (ALD) often caused by chronic heavy alcohol use and a recent period of increased alcohol consumption (i.e., a binge). It is characterized by severe inflammation and destruction of liver tissue (i.e., necrosis), potentially leading to life-threatening complications including liver failure, acute renal injury and multi-organ failure. There are no FDA approved therapies for AH and a retrospective analysis of 77 studies published between 1971 and 2016, which included data from a total of 8,184 patients, showed the overall mortality from AH was 26% at 28 days, 29% at 90 days and 44% at 180 days. A subsequent global study published in December 2021, which included 85 tertiary centers in 11 countries across 3 continents, prospectively enrolled 2,581 AH patients with a median Model of End-Stage Liver Disease (MELD) score of 23.5, reported mortality at 28 and 90 days of 20% and 31%, respectively. Stopping alcohol consumption is not sufficient for recovery in many moderate (defined as MELD scores of 11-20) and severe (defined as MELD scores >20) patients and the use of treatments to reduce liver inflammation, such as corticosteroids, are limited by contraindications and have been shown to provide no survival benefit at 90 days or 1 year. While liver transplantation is becoming more common for ALD patients, including AH patients, the procedure often involves a long waiting period, a burdensome selection process, costs exceeding $875,000 on average, and patients requiring lifelong immunosuppressive therapy to prevent organ rejection.

About Larsucosterol (DUR-928)
Larsucosterol is an endogenous sulfated oxysterol and an epigenetic regulator. Epigenetic regulators are compounds that regulate patterns of gene expression without modifying the DNA sequence. DNA hypermethylation, an example of epigenetic dysregulation, results in transcriptomic reprogramming and cellular dysfunction, and has been found to be associated with many acute (e.g., AH) or chronic diseases (e.g., NASH). As an inhibitor of DNA methyltransferases (DNMT1, DNMT3a and 3b), larsucosterol inhibits DNA methylation, which subsequently regulates expression of genes that are involved in cell signaling pathways associated with stress responses, cell death and survival, and lipid biosynthesis. This may ultimately lead to improved cell survival, reduced inflammation, and decreased lipotoxicity. As an epigenetic regulator, the proposed mechanism of action provides further scientific rationale for developing larsucosterol for the treatment of acute organ injury and certain chronic diseases.

On August 4, 2022 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported financial results for the second quarter ended June 30, 2022 and provided a corporate update (Press release, Jounce Therapeutics, AUG 4, 2022, View Source [SID1234617574]).

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"Jounce has made significant progress advancing our pipeline, and we look forward to sharing more details on our two ongoing clinical trials, INNATE and SELECT, later this year. Today, we are pleased to announce that we’ve completed enrollment in our randomized Phase 2 biomarker-selected trial SELECT, and plan to submit a clinical data abstract later this year to ESMO (Free ESMO Whitepaper)-IO being held in December. In addition, we expect to provide preliminary clinical and biomarker data across multiple cohorts from the Phase 2 portion of INNATE with an abstract submission to ESMO (Free ESMO Whitepaper)-IO in December. Our current financial position enables our continued growth and execution beyond the proof-of-concept inflection points of INNATE and SELECT, while continuing our robust, novel discovery efforts," said Richard Murray, Ph.D., chief executive officer and president of Jounce Therapeutics. "We continue to focus on our mission of delivering meaningful and long-lasting benefit to cancer patients through the discovery and pursuit of therapies that target new mechanisms of immune suppression across different types of immune cells, and bringing the right immunotherapies to the right patients."

Pipeline Update & Highlights:

JTX-8064 (LILRB2/ILT4)

Continued to advance INNATE Phase 2 trial across 7 indications. Jounce is evaluating JTX-8064 in the ongoing Phase 2 portion of the INNATE clinical trial, which is comprised of indication specific expansion cohorts, including one monotherapy cohort and seven cohorts in combination with pimivalimab. Each combination cohort is a Simon’s 2-stage design, enrolling 10 patients for an initial analysis of response data, and then further expansion to a total of 29 patients if prespecified response criteria are met. Last quarter, Jounce announced the expansion of the first two combination cohorts. The expanded indications are 3rd/4th line PD-(L)1 inhibitor naive platinum-resistant ovarian cancer and 2nd/3rd line PD-(L)1 inhibitor resistant clear cell renal cell carcinoma. Having met the response criteria for expansion, both indications are continuing enrollment to 29 patients each. Jounce has seen an acceptable safety profile for both the monotherapy and combination therapy to date.

On track to report preliminary clinical data before year end. Jounce plans to submit a clinical abstract on preliminary clinical data including all 31 Phase 1 dose escalation patients and at least 80 Phase 2 combination treatment patients from INNATE, to the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress 2022 being held from December 7-9 in Geneva, Switzerland. Phase 2 data will include safety, preliminary efficacy based on RECIST 1.1, pharmacodynamics, and potential predictive biomarker correlation with efficacy within each cohort, by prior PD-(L)1 inhibitor history, and in a cross-cohort analysis.
Vopratelimab (ICOS) and Pimivalimab (PD-1)

Patient enrollment complete in Phase 2 SELECT trial of vopratelimab. Patient enrollment is complete in the SELECT trial, a randomized Phase 2 trial evaluating vopratelimab, Jounce’s inducible costimulator (ICOS) agonist, in combination with pimivalimab versus pimivalimab alone in immunotherapy naïve, TISvopra biomarker-selected, second line non-small cell lung cancer (NSCLC) patients.

On track to report clinical data before year end. Jounce plans to submit a clinical data abstract on the SELECT trial, including additional single agent data for pimivalimab, to the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2022.

First-in-human manuscript from the ICONIC trial in Clinical Cancer Research. A manuscript was recently published in the journal Clinical Cancer Research from the Phase 1/2 ICONIC trial of vopratelimab alone and in combination with nivolumab in patients with advanced solid tumors. Data from ICONIC identified TISvopra as a potential predictive biomarker currently being investigated in SELECT.
JTX-1484 (LILRB4/ILT3)

Continued advancement of JTX-1484. JTX-1484 is the most recent product to emerge from Jounce’s Translational Science Platform and is a monoclonal antibody designed to block human LILRB4 (ILT3) expressed on myeloid cells in the tumor microenvironment with the potential to reduce immune suppression and enhance T cell functionality. JTX-1484 is currently in investigational new drug (IND) enabling activities, with the goal of filing an IND application in 2023. Jounce has submitted a preclinical abstract on JTX-1484 for consideration at this year’s annual Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) meeting being held from November 9-11 in Boston, MA.
Discovery Pipeline

LILRB family preclinical data abstract submitted to SITC (Free SITC Whitepaper). Jounce has submitted a LILRB family preclinical data abstract for consideration at this year’s SITC (Free SITC Whitepaper) annual meeting.

Productive discovery engine with the goal of an IND every 12 to 18 months. Jounce continues to invest in and advance its growing immuno-oncology pipeline. Its discovery engine is built upon the capability to thoroughly interrogate different cell types in the tumor microenvironment, including T cells and myeloid cells. This approach has resulted in four clinical stage programs, with a fifth in IND enabling studies, over the last 6 years.
Corporate Update:

Updates regarding the Board of Directors. Jigar Raythatha has become the Chair of the Board, replacing Perry Karsen who has served as the Chair since April of 2016. Perry Karsen will remain as a member of the board.

Key promotions across leadership team. Jounce is announcing that Hugh Cole is being promoted from Chief Business Officer to Chief Operating Officer, and Dr. Haley Laken is being promoted from Senior Vice President of Program and Portfolio Strategy to Chief Development Officer. Both Mr. Cole and Dr. Laken are impactful leaders within Jounce and Jounce congratulates them on their respective promotions.
Second Quarter 2022 Financial Results:

Cash position: As of June 30, 2022, cash, cash equivalents and investments decreased to $162.3 million, compared to $220.2 million as of December 31, 2021. The decrease was due to operating expenses incurred during the period.

License and collaboration revenue: Jounce did not recognize any revenue during the second quarter of 2022. License and collaboration revenue of $25.4 million was recognized during the second quarter of 2021 and was comprised of a $25.0 million clinical development and regulatory milestone for FDA clearance of the IND for GS-1811 and $0.4 million related to non-cash revenue for the performance of research and transition services, both under the Gilead License Agreement.

Research and development expenses: Research and development expenses were $26.2 million for the second quarter of 2022, compared to $22.1 million for the same period in 2021. The increase in research and development expenses was primarily due to increased manufacturing activities performed for Jounce’s development programs, increased clinical and regulatory costs for INNATE, and increased payroll and lab supplies.

General and administrative expenses: General and administrative expenses were relatively flat at $7.5 million for the second quarter of 2022, compared to $7.3 million for the same period in 2021.

Net loss: Net loss was $33.5 million for the second quarter of 2022, resulting in basic and diluted net loss per share of $0.65. Net loss was $4.0 million for the same period in 2021, resulting in a basic and diluted net loss per share of $0.08. The increase in net loss is attributable to increased operating expenses and no revenue recognized under the Gilead License Agreement in the second quarter of 2022.
Financial Guidance:

Based on its current operating and development plans and cost containment efforts, Jounce is updating its financial guidance for 2022. Gross cash burn on operating expenses and capital expenditures for the full year 2022 is now expected to be at the lower end of the range of $115.0 million to $130.0 million. Jounce now expects its existing cash, cash equivalents and investments to be sufficient to enable the funding of its operating expenses and capital expenditure requirements into the first quarter of 2024.

Conference Call and Webcast Information:

Jounce Therapeutics will host a live conference call and webcast today at 8:00 a.m. ET. To access the conference call, participants may register here1.It is advised to register at least 10 minutes prior to joining the call. The live webcast can be accessed under "Events & Presentations" in the Investors and Media section of the company’s website at www.jouncetx.com. The webcast will be archived and made available for replay on the company’s website approximately two hours after the call and will be available for 30 days thereafter.

On August 4, 2022 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported its operational and financial results for the second quarter ended June 30, 2022 (Press release, Autolus, AUG 4, 2022, View Source [SID1234617590]).

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"Autolus has had a successful second quarter, with progress made across all fronts. We were awarded Regenerative Medicine Advanced Therapy (RMAT) Designation for obecabtagene autoleucel (obe-cel) for the treatment of adult acute lymphoblastic leukemia (ALL) by the US Food and Drug Administration (FDA) in April 2022, showcased cell programming technology at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) meeting in May 2022, and announced first clinical data from four pipeline programs at the European Hematology Association (EHA) (Free EHA Whitepaper) congress in June 2022. During this time, we also continued to progress the pivotal Phase 2 FELIX clinical trial of obe-cel in r/r ALL, and the build of our commercial manufacturing site is progressing on schedule," said Dr. Christian Itin, CEO of Autolus. "Obe-cel continues to show very encouraging activity with a high level of sustained complete remissions in B-NHL patients, without inducing severe CRS or neurotoxicity, and AUTO1/22 reached clinical proof of concept with a high level of activity observed in children with ALL who are not eligible for commercial CAR T therapy. We are particularly excited about AUTO4 reaching clinical proof of concept in patients with T cell lymphoma. We are looking forward to releasing initial results for the FELIX trial in Q4 2022 and are planning updates on our other clinical studies at the end of the year."

Key Pipeline Updates:

Obecabtagene autoleucel (obe-cel) in relapsed / refractory (r/r) adult ALL
The FELIX Phase 2 trial continues to progress well, and Autolus is on track to report initial results from the trial in Q4 2022. The Company continues to expect to report full data in H1 2023, with plans to present this data at a medical conference in mid-2023.
Following the RMAT designation granted to obe-cel in April 2022 by FDA, Autolus met with the FDA to review the regulatory pathway for obe-cel in r/r ALL. Consistent with prior guidance, and assuming a positive outcome from the FELIX trial in H1 2023, the Company expects the data to form the basis of a planned Biologics License Application (BLA) submission to FDA.
As previously announced, Autolus initiated a separate cohort of up to 50 additional patients with Minimal Residual Disease (MRD), with the intention of establishing the profile of obe-cel in patients across all levels of disease burden in adult ALL.
Pipeline updates at the European Hematology Congress (EHA) (Free EHA Whitepaper), June 2022:

Obe-cel shows high level of sustained clinical activity in r/r B-NHL patients – ALLCAR19 Extension Trial
Patients continue to be enrolled into the Phase 1 ALLCAR19 extension trial. The latest data readout from this extension study of obe-cel in patients with r/r B-Cell Non-Hodgkin’s Lymphoma (B-NHL) and Chronic Lymphocytic Leukemia (CLL) were presented at EHA (Free EHA Whitepaper) in June 2022. In this patient population, obe-cel continues to display a favorable safety profile with no neurotoxicity/immune effector cell-associated neurotoxicity (ICANS) or Grade ≥ 3 Cytokine Release Syndrome (CRS). Long term persistence of obe-cel in the peripheral blood was demonstrated by qPCR. Of the 20 patients evaluable for efficacy, the overall response rate was 18/20 (90%). In the B-NHL cohorts the CRR was 16/17 (94%) (FL: 7/7, MCL: 3/3, DBCL: 6/7). In the CLL cohort 2/3 patients achieved a PR, notably both achieved MRD-negativity in their marrow and both remain in PR at 10 and 6 months respectively. Of the responding MCL, DLBCL, FL and CLL patients, 17/18 (94%) are without disease progression at last follow-up. One MCL patient relapsed six months following treatment and 1 FL patient died in CR from COVID-19. Longer follow-up and enrolment of additional MCL, FL, DLBCL and CLL patients is ongoing.
Obe-cel shows first activity in Primary CNS Lymphoma – CAROUSEL Trial
Patients continue to be enrolled into the Phase 1 CAROUSEL trial. Data from the trial were presented at EHA (Free EHA Whitepaper) in June 2022, where excellent expansion was observed in the peripheral blood by qPCR, with persistence in all treated patients at last follow-up. No Grade 3 or higher CRS was observed using IV or I-VEN AUTO1 administration. Two cases of Grade 3 ICANS were reported following IV infusion. In the first case the patient had several neurological deficits that evolved despite ICANS treatment and were compatible with progressive PCNSL, as confirmed with the month 1 MRI scan. The second case was a patient whose neurological deficits improved with steroids/anakinra. Encouraging response rates were observed: of 6 patients evaluable for efficacy following IV AUTO1, the ORR was 4/6 (67%), with 2 CRs and 2 PRs. These four responding patients are without disease progression at last follow up. Two patients died from progressive PCNSL on study.
AUTO1/22 in pediatric ALL demonstrates encouraging and durable responses in children ineligible for commercial CAR T product – CARPALL Trial
Autolus, in collaboration with UCL, continues to enroll patients into the AUTO1/22 Phase 1 CARPALL trial. The results from 11 treated patients, who were ineligible for receiving commercial CAR T therapy, were presented in an oral presentation at EHA (Free EHA Whitepaper) in June 2022. AUTO1/22 has demonstrated a favorable safety profile with no incidences of severe CRS, and one Grade 4 ICANS which was indistinguishable from chemotherapy-related leukoencephalopathy. We have seen excellent CAR T expansion, with only 4 patients losing CAR T persistence at the last follow up. Overall, 9 out of 11 patients achieved a molecular complete response, with 2 non-responders. Notably, 2 out of 3 patients with CD19-negative disease achieved molecular complete response demonstrating the efficacy of the CD22 CAR. Two patients relapsed with CD19+CD22+ disease. No antigen negative relapses were seen in responding patients. At a median follow up of 8.7 months, 6 of 9 responding patients were in MRD-negative complete remission (1-12 months) and the median duration of B-cell aplasia has not been reached.
AUTO4 shows high level of clinical activity with a novel targeting approach for patients with T Cell Lymphoma – LibrA T1 Trial
Autolus continues to enroll patients into the AUTO4 Phase 1 clinical trial. Interim Phase 1 data were presented as an oral presentation at EHA (Free EHA Whitepaper) in June 2022 from 10 patients with TRBC1-positive r/r T-cell lymphoma (Peripheral T-cell lymphoma Not Otherwise Specified (PTCL-NOS), Angioimmunoblastic T-cell lymphoma (AITL), Anaplastic Large cell lymphoma (ALCL)) in a Phase 1 dose escalation trial. The median prior lines of treatment was 3 (1-5) and three patients had prior stem cell transplantation. After lymphodepletion with Flu/Cy, patients received either 25, 75, 225 or 450 x 106 CAR T cells. AUTO4 demonstrated a tolerable safety profile, with no patient experiencing any dose limiting toxicities, and no ICANS and no Grade 3 or higher infections. CRS was only seen at the highest dose level of 450 x 106 CAR T cells (Grade 3 in 1 patient; Grade 1-2 in 3 patients). As of April 26, 2022, 9 patients were evaluable for efficacy. At the highest dose level 3 of the 3 patients dosed achieved a complete metabolic remission (CMR) at 1 month. 2 of these patients remain in ongoing CMR by PET-CT at Month 3 and 6 respectively, whilst the 3rd relapsed at 3 months.
Other pipeline updates:

AUTO8 in Multiple Myeloma – MCARTY Trial
Autolus, in collaboration with UCL, initiated a Phase 1 clinical trial of AUTO8, the Company’s next-generation product candidate for multiple myeloma, in Q1 2022, with the first patient dosed during the quarter. AUTO8 comprises two independent CARs targeting BCMA and CD19 designed to induce deep and durable responses and extend the durability of effect.
Autolus presented three abstracts at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) meeting in May 2022. The three abstracts focused on Autolus’ modular approach to CAR T product development, using innovative technology to improve our pipeline of precise, controlled and highly active products. The three abstracts covered: 1) enhancing CAR T therapy using constitutively active cytokine receptors, 2) engineering CAR T cells to express a Fas-CD40 to increase its persistence and tumor cytotoxicity and 3) developing a minocycline mediated protein-protein displacement platform to make cell therapies tunable, dose dependent and reversible.
Key Operational Updates during Q2 2022

The build phase of the Company’s new 70,000 square foot commercial manufacturing facility in Stevenage, UK continues to progress on track with the anticipated schedule. This facility is expected to be ready for Good Manufacturing Practice (GMP) operations by H2 2023 and is designed for a capacity of 2,000 batches per year with the option to expand capacity as needed.
Key Anticipated Clinical Milestones:

Initial clinical results from the pivotal FELIX Phase 2 trial in Q4 2022 and Autolus plans to present full data at a medical meeting in H1 2023.

Longer-term follow up data from Phase 1 ALLCAR19 extension trial of obe-cel in patients with r/r B-NHL and CLL planned in H2 2022.

Longer-term follow up data from Phase 1 CAROUSEL trial of obe-cel in patients with Primary CNS Lymphoma planned in 2023.

Longer-term follow up data from the Phase 1 CARPALL extension trial of AUTO1/22 in pediatric ALL patients planned in H2 2022.

Longer-term follow up data from Phase 1 LibrA T1 trial of AUTO4 in patients with Peripheral T Cell Lymphoma planned in H2 2022.

AUTO6NG Phase 1 clinical trial in patients with neuroblastoma expected to start H2 2022. First data is expected in H2 2023.

AUTO8 Phase 1 MCARTY clinical trial in patients with multiple myeloma has started, with the first patient dosed. First data is expected in H2 2023.
Financial Results for the Quarter Ended June 30, 2022

Cash at June 30, 2022, totaled $216.4 million, as compared to cash of $310.3 million at December 31, 2021.

Total operating expenses for the three months ended June 30, 2022, were $46.5 million, as compared to total operating expenses, net of grant income and license revenue of $1.6 million, of $37.7 million for the same period in 2021.

Research and development expenses increased by $6.1 million to $38.2 million from $32.1 million for the three months ended June 30, 2022 as compared to the same period in 2021. The net increase in research and development expenses of $6.1 million was primarily due to:

an increase of $3.5 million in clinical costs and manufacturing costs primarily relating to the obe-cel clinical product candidate,
an increase of $1.4 million in salaries and other employment related costs including share-based compensation expense, which is mainly driven by an increase in the number of employees engaged in research and development activities,
an increase of $1.4 million in legal fees and professional consulting fees in relation to the Company’s research and development activities,
an increase of $0.5 million related to information technology infrastructure and support for information systems related to the conduct of clinical trials and manufacturing operations,
a decrease of $0.5 million in facilities costs related to the termination and closure of the Company’s US manufacturing facility in 2021 and shift in its manufacturing strategy, and
a decrease of $0.2 million in depreciation and amortization related to property, plant and equipment and intangible assets.
General and administrative expenses increased by $1.1 million to $8.3 million for the three months ended June 30, 2022 from $7.2 million for the three months ended June 30, 2021 primarily due to:

an increase of $1.3 million in salaries and other employment related costs including share-based compensation expenses, which was mainly driven by an increase in the number of employees engaged in general and administrative activities,
an increase of $0.1 million primarily related to higher directors’ and officers’ liability insurance premiums, professional fees and information technology costs,
a decrease of $0.2 million in facilities costs related to the termination by the Company of certain lease agreements in the prior year, and
a decrease of $0.1 million in depreciation and amortization related to property, plant and equipment and intangible assets.
Other expense, net decreased by $0.5 million to $1.3 million for the three months ended June 30, 2022 from $1.8 million for the three months ended June 30, 2021, relating primarily due to the strengthening of the U.S. dollar exchange rate relative to the pound sterling.

Interest expense increased to $1.8 million for the three months ended June 30, 2022 and relates to the liability related to sales of future royalties and sales milestones which arose upon the Company’s entry into the strategic collaboration and financing agreement with Blackstone, in November 2021. There was no interest expense during the comparable period in 2021.

Income tax benefit increased by $1.1 million to $7.5 million for the three months ended June 30, 2022 from $6.4 million for the three months ended June 30, 2021 due to an increase in qualifying research and development expenditures for the quarter.

Net loss attributable to ordinary shareholders was $42.1 million for the three months ended June 30, 2022, as compared to $33.2 million for the same period in 2021. The basic and diluted net loss per ordinary share for the three months ended June 30, 2022, totaled $(0.46) compared to a basic and diluted net loss per ordinary share of $(0.47) for the three months ended June 30, 2021.

Autolus estimates that its current cash on hand and anticipated milestone payments from Blackstone extends the Company’s runway into 2024.

Conference Call
Management will host a conference call and webcast at 8:30 am ET/1:30 pm BST to discuss the Company’s financial results and provide a general business update. Conference call participants should pre-register using this link to receive the dial-in numbers and a personal PIN, which are required to access the conference call. The conference call system has changed, so please make sure you dial in 15 minutes before to ensure timely access to the call.

A simultaneous audio webcast and replay will be accessible on the events section of Autolus’ website.

On August 4, 2022 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company developing a novel class of injectable biologics to selectively engage and modulate tumor-specific T cells directly within the patient’s body, reported second quarter 2022 financial results (Press release, Cue Biopharma, AUG 4, 2022, View Source [SID1234617706]). The Company will host a business update call and webcast on Tuesday, August 23, 2022 at 4:30 p.m. EDT. Live and archived versions of the event can be accessed via the Company’s website.

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Recent Business Updates

Investigational New Drug (IND) application accepted by the U.S. Food and Drug Administration (FDA) for CUE-102 in Wilms’ Tumor 1 (WT1) expressing cancers. Based on the premise that CUE-102 possesses the same molecular framework as CUE-101 except for the nine amino acid sequence difference between HPV-E7 and WT1, the IND was supported by clinical and safety data from the ongoing CUE-101 monotherapy trial and did not require additional IND-enabling toxicology studies.
Initiated a dose escalation monotherapy Phase 1 trial with CUE-102 at a starting dose of 1mg/kg. The trial will focus on patients with WT1-positive recurrent/metastatic gastric, pancreatic, ovarian and colorectal cancers.
Presented interim CUE-101 clinical data at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) on June 6th. Eight of the nine evaluable patients treated with CUE-101 and KEYTRUDA in the dose escalation portion of our combination study had at least one post dose scan at the time of the data cut-off of April 22. Of the eight patients, two patients, one patient at the 2mg/kg dose and one patient at the 4mg/kg dose, had confirmed ongoing partial responses and two additional patients had durable stable disease, defined as stable disease on at least two consecutive post-treatment scans lasting at least 12 weeks.
Extended cash runway with an aggregate of $23.6 million, net of commissions paid, from the sale of 3,593,407 shares of our common stock pursuant to our ATM equity offering sales agreement with Jefferies LLC during the first six months of 2022.
"As we continue to progress the IL-2-based CUE-100 series for oncology, our confidence is bolstered by the growing body of evidence that our Immuno-STAT platform and therapeutic approach appear to represent a potential breakthrough in oncology," said Daniel Passeri, chief executive officer of Cue Biopharma. "We are encouraged with the continued progress of the CUE-101 monotherapy and combination trials and look forward to providing a business update during our upcoming call. We are also pleased with the recent acceptance of the IND for the CUE-102 Phase 1 dose escalation trial, which importantly will begin at 1mg/kg dose, as compared to 0.16mg/kg in the Phase 1 dose escalation of CUE-101 saving us valuable time and resources in determining the tolerability and recommended Phase 2 dose of CUE-102. In summary, we are very pleased with our clinical trial progress and associated data to date as we continue to further the clinical development of our CUE-100 series pipeline throughout fiscal year 2022."

Kerri-Ann Millar, chief financial officer of Cue Biopharma added, "During the second quarter of 2022, management took proactive steps to decrease the Company’s office and lab footprint and restructure in support of newly prioritized corporate objectives and strategies. These important steps, resulting in a significant cost savings that has been allocated to key clinical programs, coupled with successfully accessing our at-the-market (ATM) common stock facility will allow us to assess the data readouts from our CUE-101 Phase 1 monotherapy and combination clinical trials."

Second-Quarter 2022 Financial Results
The Company reported collaboration revenue of approximately $26 thousand and $2.7 million for the three months ended June 30, 2022 and 2021, respectively.

Research and development expenses were $9.6 million and $8.8 million for the three months ended June 30, 2022 and 2021, respectively. The increase in research and development expenses of $0.8 million was primarily due to an increase in laboratory and drug substance manufacturing costs, employee compensation, other professional fees, licensing fees, and rent.

General and administrative expenses were $3.8 million and $4.3 million for the three months ended June 30, 2022 and 2021, respectively. The decrease in general and administrative expense of $0.5 million was primarily due to a decrease in stock-based compensation expense related to executive management, professional and consulting fees, and employee and board compensation incurred in the second quarter of 2022 as compared to the same period in 2021.