On December 13, 2021 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported updated interim clinical data from the ongoing Phase 1/2 CIRLL (Cirmtuzumab and Ibrutinib targeting ROR1 for Leukemia and Lymphoma) clinical trial, that will be presented in a poster presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2021 Annual Meeting (Press release, Oncternal Therapeutics, DEC 13, 2021, View Source [SID1234596937]). In the CIRLL study, zilovertamab, an investigational anti-ROR1 monoclonal antibody, is being evaluated in combination with ibrutinib in patients with MCL and CLL. The clinical trial is being conducted in collaboration with UC San Diego and is partially funded by the California Institute for Regenerative Medicine (CIRM).

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The updated interim data will be presented as a poster presentation at the Mantle Cell, Follicular and Oher Indolent B Cell Lymphomas Clinical and Epidemiological session on December 13, 2021 as part of the ASH (Free ASH Whitepaper) 2021 Annual Meeting:

Poster Title: Phase 1/2 Study of Cirmtuzumab and Ibrutinib in Mantle Cell Lymphoma (MCL) or Chronic Lymphocytic Leukemia (CLL)
Publication Number: 3534
Session Name: 623, Mantle Cell, Follicular and Oher Indolent B Cell Lymphomas Clinical and Epidemiological
Session Date and Time: December 13, 2021 from 6:00-8:00 pm (Eastern Time)
Location: Georgia World Congress Center, Hall B5
"Our confidence in the differentiation of zilovertamab enabled therapy continues to build as we strengthen our MCL and CLL data set. The median PFS of 35.9 months for heavily pre-treated MCL patients is approximately three times longer than the previously reported median PFS of 12.8 months for ibrutinib monotherapy. The landmark PFS of 85% at 24 months and 65% at 36 months for patients with CLL, regardless of the number of prior lines of therapy, are also encouraging. The combination continues to be generally well tolerated, and we are encouraged by the low grade 3/4 neutropenia rate of 10% for the combination therapy, compared to 29% for ibrutinib alone from its registration study in MCL," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "We expect to provide an update regarding our dialogue with the U.S. FDA regarding Phase 3 study design later this month."

The results that will be presented in poster form at ASH (Free ASH Whitepaper) 2021 include 31 patients with relapsed/refractory MCL enrolled in the dose-finding and dose-expansion cohorts of the CIRLL clinical trial (Part 1 + Part 2), of whom 26 were evaluable for efficacy as of the October 1, 2021 data cut-off date.

Patients had high-risk factors and were heavily pre-treated at study entry, with 52% having high Ki-67 proliferative index (≥30%) and 45% with intermediate/high sMIPI prognostic score.
The ORR of 81% (21 of 26 evaluable patients), including recently enrolled patients with relatively short follow-up time, is comparable to the 83% ORR (15 of 18 evaluable patients) previously presented at the ASCO (Free ASCO Whitepaper) 2021 Annual Meeting.
Twelve of 26 (46%) evaluable patients achieved a partial response (PR) and three patients (12%) had stable disease (SD), for a total clinical benefit rate (CR, PR and SD) of 92%.
The complete response rate was 35% (9 of 26 evaluable patients). CRs have remained durable, for up to 32 months as of the data cutoff date.
The ORR and median duration of response were favorable in patients with high-risk features associated with difficult to treat disease:
Ki-67 ≥30%: ORR of 85%; median duration of response of 14 months (95% CI: 13.7, NE), and
>1 prior systemic therapy: ORR of 82%; median duration of response not reached for patients receiving two prior lines of systemic therapy and 34 months (95% CI: 13.8, 34.1) for patients with ≥ 3 prior lines of systemic therapy
Five patients had received prior treatment with ibrutinib, achieving two CRs and two PRs. One patient had SD.
Median PFS was 35.9 months after a median follow-up of 14.4 months (95% CI: 11.4, 19.3), regardless of number of prior systemic therapies. Further, median PFS had not been reached for patients achieving a CR.
Historical data published for single agent ibrutinib for 370 patients with relapsed/refractory MCL from three clinical trials showed an ORR of 66%, CR rate of 20% and median PFS of 12.8 months (Rule et al. 2017, British Journal of Haematology).
As of the October 1, 2021 data cut-off date, 34 patients with CLL have been enrolled in the dose-finding and dose-confirming cohorts of this clinical trial (Part 1 & Part 2), all of which were evaluable for efficacy. Patients had high-risk factors, and most were heavily pre-treated at study entry, with 71% having RAI staging ≥2 and a median of two systemic prior therapies (range 1-15).

The ORR was 91% (31 of 34 evaluable patients), consistent with prior published results.
The CR rate was 6% (2 of 34 evaluable patients), twenty-nine patients (85%) achieved a PR and three patients (9%) had SD, for a total clinical benefit rate (CR, PR and SD) of 100%.
Median PFS in patients with ≤ 2 prior therapies had not been reached, and patients with > 2 prior therapies had a median PFS of ~36.1 months after a median follow up of 29.0 months (95% CI: 27.6, 31.6), in this high risk and mostly heavily pre-treated CLL population.
Based on the Kaplan-Meier curve, landmark PFS of ~ 85% and ~ 65% at 24 and 36 months, respectively, for CLL patients receiving > 2 prior lines of therapy compared favorably to historical ibrutinib monotherapy of ~ 65% and ~ 50%, respectively (Byrd 2019). Landmark PFS was 100% at 36 months for CLL patients with ≤ 2 prior lines of therapy, which compares favorably to historical ibrutinib monotherapy of ~ 75% (Byrd 2019).
Thirty-one patients with CLL have also been enrolled in the randomized efficacy cohort of this clinical trial (Part 3), of which 22 were evaluable for efficacy. Data on this cohort is maturing, and median PFS had not been reached as of the October 1, 2021 cut-off date.

The combination of zilovertamab plus ibrutinib has been well tolerated, with treatment emergent adverse events consistent with those reported for ibrutinib alone. There have been no dose-limiting toxicities and no serious adverse events attributed to zilovertamab alone.

About the CIRLL Clinical Trial
The CIRLL clinical trial (CIRM-0001) is a Phase 1/2 trial evaluating zilovertamab in combination with ibrutinib in separate groups of patients with CLL or MCL. Enrollment of the dose-finding cohorts in CLL and MCL, dose-expansion cohort in CLL and randomized Phase 2 cohort in CLL has been completed. Enrollment of the dose-expansion cohort in MCL is ongoing. Additional information about the CIRM-0001 clinical trial and other clinical trials of zilovertamab may be accessed at ClinicalTrials.gov.

About Zilovertamab (formerly Cirmtuzumab)
Zilovertamab is an investigational, potentially first-in-class monoclonal antibody targeting ROR1, or Receptor tyrosine kinase-like Orphan Receptor 1. Zilovertamab is currently being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of MCL or CLL, in a collaboration with the University of California San Diego (UC San Diego) School of Medicine and the California Institute for Regenerative Medicine (CIRM). In addition, Oncternal is supporting two investigator-sponsored studies being conducted at the UC San Diego School of Medicine: (i) a Phase 1b clinical trial of zilovertamab in combination with paclitaxel for the treatment of women with HER2-negative metastatic or locally advanced, unresectable breast cancer, and (ii) a Phase 2 clinical trial of zilovertamab in combination with venetoclax, a Bcl-2 inhibitor, in patients with relapsed/refractory CLL.

ROR1 is a potentially attractive target for cancer therapy because it is an onco-embryonic antigen – not usually expressed on adult cells, and its expression confers a survival and fitness advantage when reactivated and expressed by tumor cells. Researchers at the UC San Diego School of Medicine discovered that targeting a critical epitope on ROR1 was key to specifically targeting ROR1 expressing tumors. This led to the development of zilovertamab, that binds this critical epitope of ROR1, which is highly expressed on many different cancers but not on normal tissues. Preclinical data showed that when zilovertamab bound to ROR1, it blocked Wnt5a signaling, inhibited tumor cell proliferation, migration and survival, and induced differentiation of the tumor cells. The FDA has granted Orphan Drug Designations to zilovertamab for the treatment of MCL and CLL/small lymphocytic lymphoma. Zilovertamab is in clinical development and has not been approved by the FDA for any indication.

On December 13, 2021 Boston Immune Technologies and Therapeutics, Inc. (BITT), a privately held developer of novel tumor necrosis factor (TNF) Superfamily antagonist antibodies, reported that the company has received a Small Business Innovation Research (SBIR) grant from the National Cancer Institute at the U.S. National Institutes of Health (Press release, BITT, DEC 13, 2021, View Source [SID1234596968]). The award is for a project titled "Preclinical Toxicology and Pharmacology Evaluation of a New TNFR2 Antagonistic Monoclonal Antibody for Cutaneous T Cell Lymphoma (CTCL) Therapy." The company also announced that Bruce Beutel, Ph.D., has joined BITT’s Board of Directors.

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"The SBIR funding will be used to complete the IND-enabling steps and initiate clinical trials of our anti-TNFR2 antibody, BIR2101," said Russell LaMontagne, Co-Founder and Chief Executive Officer of BITT. "We appreciate the recognition of our unique approach to TNFR2 antagonism and the importance of TNFR2 as novel target in cancer immunotherapy."

Dr. Beutel has over 25 years of leadership experience in drug discovery and business development. Before joining BITT, he was founding chief operating officer of Dewpoint and entrepreneur in residence at the LS Polaris Innovation Fund. His prior roles have also included chief business officer at SQZ Biotechnologies and executive director at Merck.

On December 13, 2021 Curaleaf Holdings, Inc. (CSE: CURA /OTCQX: CURLF) ("Curaleaf" or the "Company"), a leading international provider of consumer products in cannabis, reported that it has received commitments for a private placement of 8.0% Senior Secured Notes due 2026 (the "Notes") for aggregate gross proceeds of US$425 million (the "Offering") (Press release, Curaleaf Holdings, DEC 13, 2021, View Source [SID1234596989]).

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The Notes, which will be issued at 100% of face value, will be senior secured obligations of the Company and will bear interest at a rate of 8.0% per annum, payable semi-annually in equal installments until the maturity date, unless earlier redeemed or repurchased. The Notes will be governed by a trust indenture to be entered into on closing of the Offering (the "Indenture"). The Indenture enables the Company to issue additional notes on an ongoing basis as needed, subject to maintaining leverage ratios and complying with the other terms and conditions of the Indenture. In addition, the Indenture permits up to an additional US$200 million of senior bank financing. Curaleaf intends to use the net proceeds from the Offering to refinance existing indebtedness, for working capital, and to pay transaction fees and expenses. The Notes will mature on December 15, 2026. The Offering is expected to close on December 15, 2021, subject to customary closing conditions.

"We are pleased to announce what we believe is the largest debt financing of any publicly-traded MSO to date," said Joseph Bayern, Chief Executive Officer of Curaleaf. "This offering will allow us to refinance our existing debt at a materially lower interest rate and provides us with additional financial flexibility to execute our strategic growth initiatives. While this initial offering provides more than enough liquidity to refinance our existing debt and meet current needs, the new Indenture provides us a new degree of flexibility to raise debt financing to ensure we have ample liquidity to meet our needs now and into the future."

Seaport Global Securities LLC and Canaccord Genuity Corp. (the "Agents") acted as placement agents for the Notes in the United States and Canada, respectively.

The Notes are being offered on a private placement basis in certain provinces and territories of Canada pursuant to applicable exemptions from the prospectus requirements of Canadian securities laws. The Notes may also be sold in the United States to or for the account or benefit of "U.S. persons" (as defined in the United States Securities Act of 1933, as amended (the "U.S. Securities Act")), on a private placement basis to "qualified institutional buyers" and "accredited investors" pursuant to an exemption from the registration requirements of the U.S. Securities Act, and in such jurisdictions outside of Canada and the United States as may be agreed upon by the Agents and the Company, in each case in accordance with applicable laws. The Notes to be issued will be subject to a customary four-month hold period under Canadian securities laws.

No securities regulatory authority has either approved or disapproved of the contents of this news release. The Notes have not been and will not be registered under the U.S. Securities Act or any state securities laws. Accordingly, the Notes may not be offered or sold within the United States or to or for the account or benefit of "U.S. persons" unless registered under the U.S. Securities Act and applicable state securities laws or pursuant to exemptions from the registration requirements of the U.S. Securities Act and applicable state securities laws. This news release does not constitute an offer to sell or a solicitation of an offer to buy any securities of the Company in any jurisdiction in which such offer, solicitation or sale would be unlawful.

On December 13, 2021 ERYTECH Pharma (Nasdaq & Euronext: ERYP), a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, reported a summary of its poster presentation at the 2021 ASH (Free ASH Whitepaper) Annual Meeting evaluating GRASPA (eryaspase) in acute lymphoblastic leukemia (ALL) as well as the acceptance of two abstracts evaluating eryaspase in advanced pancreatic cancer at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI), which will be held January 20-22, 2022, both in San Francisco, CA and virtually (Press release, ERYtech Pharma, DEC 13, 2021, View Source [SID1234597045]).

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On December 13, 2021 Harpoon Therapeutics, Inc. (NASDAQ: HARP), a clinical-stage immunotherapy company developing novel T cell engagers, reported a pipeline update on its programs, including the interim data presented from the ongoing dose-escalation portion of the Phase 1/2 trial for HPN217 in patients with relapsed/refractory multiple myeloma (R/R MM) at the 63rd American Society for Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, Harpoon Therapeutics, DEC 13, 2021, View Source [SID1234597098]). Harpoon has four product candidates in clinical trials that are based on its proprietary Tri-specific T cell Activating Construct (TriTAC) platform designed to recruit a patient’s own immune cells to kill tumor cells.

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"We are focused on advancing our clinical programs in 2022 and are pleased to see the HPN217 and HPN328 programs showing clinical activity at well tolerated dose levels, indicating a threshold effect," stated Julie Eastland, President and CEO, Harpoon Therapeutics. "We look forward to the initiation of expansion cohorts to learn more about these promising TriTAC programs while building our future clinical pipeline with our first ProTriTAC candidate, HPN601 targeting EpCAM, currently in IND-enabling studies."

"The interim clinical data from the escalation portion of the HPN217 trial shows robust anti-myeloma activity that is encouraging," said Natalie Sacks, M.D., Chief Medical Officer of Harpoon. "In addition, we are observing tumor shrinkage in small lung cancer patients in the HPN328 trial, and we are excited to see validation of the TriTAC platform in both solid tumors and hematologic malignancies. We continue to investigate the performance of our novel technology in multiple indications and are encouraged by the signs of clinical activity and manageable tolerability profiles."

Dose escalation for HPN217 (BCMA TriTAC) Phase 1/2 clinical trial Ongoing
Relapsed/refractory multiple myeloma patients (N=37) have been treated across 9 fixed dose cohorts of 5 to 2860 µg/week, and 1 step dose cohort of 1620 (priming) and 3240 (target) µg/week reflecting rapid dose expansion since the trial began. HPN217 has been well tolerated, with one DLT, Grade 4 AST which resolved, as of the November 10, 2021 data cutoff date.

The ASH (Free ASH Whitepaper) poster presentation, included the following observations:

Encouraging clinical activity in higher dose cohorts including a 63% ORR and 88% DCR reported in the 2150 µg/week cohort with 8 disease evaluable patients with R/R MM, including one minimal residual disease (MRD) negative, stringent CR.
HPN217 shows tolerable safety profile with cytokine release syndrome (all Grade 1 or 2) observed in 9 of 37 patients (24%)
Patient enrollment and dose escalation is ongoing to define the RP2D and MTD
Introduction of step dose regimens has allowed for the administration of higher target doses.
Dose escalation for HPN328 (DLL3 TriTAC) Phase 1/2 clinical trial making rapid progress. Fifteen patients have been enrolled in dose cohorts ranging from 15 µg to 7200 µg per week in both fixed and step dose cohorts administered once weekly by intravenous infusion. Fifteen patients with a median of 2 lines (range 1 to 5) of prior therapy have been enrolled and eligible patients include small cell lung cancer patients who have relapsed after platinum chemotherapy and patients with other malignancies with high grade neuroendocrine tumors associated with DLL3 expression. HPN328 has been well tolerated with Grade 1-2 CRS reported in 33% of patients, no DLTs observed and MTD has not been reached. Among four patients with small cell lung cancer receiving the two highest doses tested to date, 1215 µg fixed dose and 3600-7200 µg step dose, three had target lesion reduction, including 1 confirmed RECIST partial response. The patient with a cPR experienced a target lesion reduction of 53% at week 10. Presentation of initial interim clinical data is planned for 2022.

IND-enabling studies for HPN601 (EpCAM ProTriTAC) are progressing as planned. HPN601 is the first conditionally active T cell engager based on the ProTriTAC platform. EpCAM is expressed in a broad range of solid tumors, including gastrointestinal cancers, potentially enabling HPN601 to address multiple indications with high unmet medical need. By the end of 2022, an IND submission for HPN601 is expected as well as identification of a second IND candidate from the ProTriTAC platform.

Harpoon’s T cell engager platforms, TriTAC, ProTriTAC, and TriTAC XR, are designed to mitigate different target toxicities across a range of disease indications, including solid and hematologic malignancies.

Next generation T cell engager platforms advancing. Harpoon continues to discover new technologies to improve the therapeutic application of T cell engagers. We recently introduced the TriTAC XR platform, which is designed to minimize on-target cytokine release syndrome. Nomination of an IND candidate from the TriTAC XR platform is also expected by the end of 2022.

Conference Call and Webcast Today

Harpoon’s management will host a webcast and conference call at 4:30 p.m. ET / 1:30 p.m. PT on Monday, December 13, 2021 to review the data presented at ASH (Free ASH Whitepaper) and provide an update on its other pipeline programs. The live call may be accessed by dialing 866-951-6894 for domestic callers or 409-216-0624 for international callers and using conference ID # 2760075.

A live webcast of the call will be available from the Events and Presentations section of the company’s website at View Source and will be archived there shortly after the live event.