On October 23, 2023 Mereo BioPharma Group plc (NASDAQ: MREO) ("Mereo" or the "Company"), a clinical-stage biopharmaceutical company focused on rare diseases, reported an update on recent program developments and third quarter 2023 financial information (Press release, Mereo BioPharma, OCT 23, 2023, View Source [SID1234636252]).

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Recent Program Developments

Setrusumab (UX143)

On October 14, 2023, Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) and Mereo BioPharma Group plc ("Mereo" or the "Company") announced interim data from the Phase 2 portion of the Phase 2/3 Orbit study demonstrating that treatment with setrusumab (UX143) achieved a 67% reduction in annualized fracture rate in patients with osteogenesis imperfecta (OI) with at least 6 months of follow-up and continues to demonstrate ongoing and meaningful improvements in lumbar spine bone mineral density (BMD). The Phase 3 portion of the study is currently enrolling approximately 195 patients at 50 sites across 12 countries.

Alvelestat (MPH-966)

University of Alabama at Birmingham (UAB) and the Company are reporting on the ATALANTa study, a multi-center, double-blind, placebo-controlled, proof-of-concept investigator-led study run by Professor Mark Dransfield, Director of the Division of Pulmonary, Allergy and Critical Care, UAB, in collaboration with Mereo. ATALANta investigated the safety and efficacy of alvelestat 120 mg, or matched placebo, twice daily, for 12 weeks in a broad range of individuals with Alpha-1 Antitrypsin Deficiency-Associated Lung Disease, including subjects with less severe phenotypes (Pi*SZ) than were enrolled in the Company-sponsored ASTRAEUS Phase 2 study, and those receiving augmentation therapy. The study randomized 63 patients, 32 in the 120 mg alvelestat arm (44% on augmentation therapy) and 31 in the placebo arm (48% on augmentation therapy).

The results demonstrated with the 120 mg dose of alvelestat (the lower dose used in the Phase 2 ASTRAEUS study) are consistent with those observed in ASTRAEUS on blood neutrophil elastase activity and changes in the biomarkers desmosine and Aα-val360. The data from ATALANTa also show the significant effect of alvelestat on the SGRQ-activity domain in patients not on augmentation (p=0.0106 versus placebo).

There was no difference in the proportion of patients with treatment-related Adverse Events (AEs) between the alvelestat and placebo arms. There were no Serious Adverse Events (SAEs) and no Adverse Events of Special interest (AESIs) of liver, QTC prolongation or neutropenia observed. AESIs of infection were more frequent in the placebo arm, driven by an increased number of acute exacerbations of COPD (one in the alvelestat arm in a patient on augmentation, and seven exacerbations in the placebo arm in seven patients, five of whom were on augmentation). There were two discontinuations in the alvelestat group due to mild and moderate headache. The data demonstrate that the 120 mg dose of alvelestat is safe on top of augmentation and support Mereo’s selection of the 240 mg dose to be studied in the planned Phase 3 pivotal trial. Additional data are expected to be presented by UAB at future medical conferences.

The ATALANTa study was funded by the National Center for Advancing Translational Sciences (NCATS) through the National Institutes of Health (NIH)-Industry Program for discovering new therapeutic uses for existing molecules.

In Europe, the Company has received guidance from the European Medicines Agency (EMA) that a Phase 3 primary endpoint of lung density by computed tomography (CT) scan with a relaxed p value (p<0.1) may, if the study is successful, be sufficient for full approval. In the US, the Company is continuing its interactions with the FDA and the Division of Clinical Outcomes Assessment (DCOA) regarding the use of a Patient Reported Outcome (PRO) as a primary Phase 3 endpoint.

The data from the ATALANTa study are expected to further support the ongoing partnering process for the alvelestat Phase 3 program.

Etigilimab (MPH-313)

On October 21, 2023, an update on the Company’s Phase 1b/2 study investigating the safety and efficacy of etigilimab (anti-TIGIT) in combination with nivolumab (anti-PD1) in recurrent/advanced solid tumors (ACTIVATE) was presented in a mini-oral session at the ESMO (Free ESMO Whitepaper) 2023 Congress in Madrid, Spain by Dr. Meredith McKean, Sarah Cannon Research Institute, USA. Of 40 evaluable patients presented in select cohorts, three complete responses (CRs), seven partial responses (PRs) and eleven stable disease (SDs) beyond 112 days (3.7 months) were noted. Seven patients showed clinical benefit for ≥ 335 days (11 months). The data show promising efficacy in PDL1 low patients with six of seven on study ≥ 335 days (11 months) being PDL1 negative or low and all having high PVR tumoral expression. Etigilimab in combination with nivolumab continues to be safe and well tolerated with no new safety signals noted. The last patient last dose was completed at the end of June 2023. The cervical cancer and uveal melanoma cohorts cleared the protocol Simon 2 Stage design interim futility monitoring bar for expansion to Stage 2 and were endorsed by an independent data monitoring committee for expansion.

Etigilimab, in combination with nivolumab, is in an ongoing investigator-led single-arm, two-stage, open-label Phase 1b/2 trial in a subtype of platinum-resistant recurrent ovarian cancer (clear cell ovarian cancer) at The University of Texas MD Anderson Cancer Center, financed by the Cancer Focus Fund. This trial is being led by Dr. Shannon Westin. Enrollment is currently being expanded from the initial 10 patients to 20 patients.

The Company continues to seek a partner for further development of etigilimab.

Third Quarter 2023 Financial Information

As of September 30, 2023, the Company had cash and short-term deposits of £51.2 million ($62.4 million). Cash and short-term deposits, net of expenditures, increased by £9.1 million ($11.1 million) during the third quarter of 2023.

In July 2023, the Company received a $9.0 million (£7.1 million) milestone payment from its partner, Ultragenyx, and gross proceeds of $12.0 million (£9.3 million) from the issuance of 9,673,419 ADSs representing 48,367,095 ordinary shares through an "at-the-market" offering pursuant to its Open Market Sale Agreement with Jefferies LLC. The Company expects its existing cash and short-term deposits, excluding income from existing or potential partnerships, will enable it to fund its currently committed clinical trials, operating expenses and capital expenditure requirements into 2026.

On October 23, 2023 Kiromic BioPharma, Inc. (OTC PINK: KRBP) ("Kiromic" or the "Company"), a clinical-stage, fully-integrated biotherapeutics company using its proprietary DIAMOND artificial intelligence and data mining platform to develop cell therapies with a focus on immuno-oncology, reported the execution of a clinical trial agreement with Beverly Hills Cancer Center (BHCC) to conduct its Deltacel-01 Phase 1 Study (Press release, Kiromic, OCT 23, 2023, View Source [SID1234636251]). Pursuant to the agreement, BHCC, one of Southern California’s esteemed private cancer centers, is anticipated to serve as the inaugural clinical site for the evaluation of Deltacel (KB-GDT-01), Kiromic’s allogeneic, off-the-shelf, Gamma Delta T-cell (GDT) therapy, in patients with non-small cell lung cancer (NSCLC).

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The collaboration between Kiromic BioPharma and BHCC underscores the shared commitment between the two organizations to advance the fight against cancer through innovative therapeutic approaches. BHCC is a private, comprehensive facility which includes a radiation oncology center, an infusion center, a full-service diagnostic imaging center (featuring MRI, CT, PET/CT), and a diagnostic laboratory, and has a distinguished history of conducting clinical trials across multiple cancer types.

"As our clinical research program embarks on this groundbreaking clinical journey, we envision a future where patients have access to pioneering therapies and renewed hope in their battle against cancer. For years, BHCC has remained at the forefront of medical excellence, continually seeking innovative approaches to redefine the future of cancer treatment. We are very excited about this collaboration with Kiromic, a very forward-thinking and innovative company, and about this new therapeutic approach and the potential to contribute to science with the ultimate goal of improving the lives of cancer patients worldwide," said Afshin Eli Gabayan, MD, Medical Director and Principal Investigator at Beverly Hills Cancer Center and Assistant Clinical Professor at UCLA-David Geffen School of Medicine.

"The clinical trial agreement is a momentous first step in the development of this important treatment. BHCC is our first clinical site from a timeline perspective and has a history of high-quality clinical research and exceptional patient care, and it represents an ideal setting for a rigorous evaluation of our cell therapy candidate," stated Pietro Bersani, Kiromic Chief Executive Officer. "We are also actively engaging and making continued progress with other prestigious clinical trial sites to expand the reach and the impact of this study across a total of up to four sites. We intend to provide updates on the progress of the Deltacel-01 clinical study, including subsequent site activations, as the trial advances."

NSCLC is the most prevalent type of lung cancer, representing about 80% to 85% of lung cancer cases. Lung cancer is by far the leading cause of cancer death in the U.S., accounting for about 1 in 5 of all cancer deaths.

On October 23, 2023 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported that selected clinical data from the company’s ongoing Phase 1 clinical trial evaluating EVT801 in patients with advanced solid tumours was presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 (ESMO 2023) on Saturday, 21 October 2023 (Press release, Kazia Therapeutics, OCT 23, 2023, View Source [SID1234636250]).

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Professor Carlos A Gomez-Roca, (IUCT-Oncopole, Toulouse France) presented data from a correlation analysis of tumour biopsies from six (6) enrolled patients with high grade serous ovarian cancer (HGS-OC). To date, twenty (20) patients with advanced solid tumors have been dosed in in the ongoing Phase 1 clinical trial, and the trial has advanced to dose escalation cohort 6.

Key Points from the presentation:

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The hypothesis for EVT801’s mechanism of action involves three (3) sequential anti-cancer mechanisms, all of which are thought to contribute to the potential inhibition of tumour growth and metastasis:

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Preventing tumour growth by impairing both tumour angiogenesis and (lymph)angiogenesis, thereby stabilizing the tumour vasculature, reducing metastasis, and reducing hypoxia in the tumour microenvironment.

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Enhancing anti-cancer immunity as reflected by a decrease in immunosuppressive cytokines and cells in the circulation and tumour environment.

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Promoting T-cell infiltration into the tumour, ultimately supporting an enhanced and long-lasting anti-tumour immune response.

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In a data analysis of biopsies from six (6) HGS-OC patients, high levels of VEGFR3 expression tended to be correlated with the following:

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Higher levels of hypoxia;

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Increased immune checkpoint (PD1) resistance; and

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Negatively correlated with CD8 positive T-cells infiltration.

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While these findings would need to be confirmed in patients in other indications, these correlations are encouraging and suggest that patients with hypoxic HGS-OC tumours that are poorly infiltrated with CD8 positive T-cells and with high VEGFR3 expression may benefit from EVT801 treatment.

"In spite of recent advances in treatments for ovarian cancer, there is an extremely high rate of recurrence. The success of immune checkpoint inhibitors in other solid tumours has not carried through to high grade serous ovarian cancer. In data previously presented at AACR (Free AACR Whitepaper) 2023, we demonstrated a high prevalence of VEGFR-3 expression in HGS-OC tumours, and we have now presented data showing a positive correlation between VEGFR-3 expression and hypoxia and PD1 resistance signature and a negative correlation with CD8 positive T-cell infiltration," said Dr. John Friend, Chief Executive Officer of Kazia. "We look forward to completing dose escalation in stage 1 of the ongoing study and progressing to stage 2 of the Phase 1 Study ."

On October 23, 2023 Inspirna, Inc., a clinical stage biopharmaceutical company developing first-in-class cancer therapeutics, reported data from the ongoing Phase 1b/2 study of ompenaclid (RGX-202) in combination with FOLFIRI and bevacizumab (BEV) in RAS-mutated (RASm) advanced or metastatic colorectal cancer (CRC) presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 being held October 20-24, 2023 in Madrid, Spain (Press release, Inspirna, OCT 23, 2023, View Source [SID1234636249]).

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"We are excited to share the clinical data being presented at ESMO (Free ESMO Whitepaper), further demonstrating the clear potential of ompenaclid to improve on the standard-of-care for advanced CRC, especially for the approximately 40-45% of CRC patients whose tumors harbor a RAS mutation," said Andrew Hendifar, M.D., Assistant Professor of Medicine at Cedars-Sinai Medical Center and Principal Investigator on the study. "Encouraging efficacy was observed in patients with RASm second-line metastatic CRC with a response rate exceeding that expected with the standard-of-care regimen FOLFIR/BEV alone. At the evaluated dose levels, ompenaclid plus FOLFIRI/BEV was also well tolerated and induced potent inhibition of SLC6A8, consistent with preclinical and previously presented Phase 1 data."

Ompenaclid is a first-in-class oral inhibitor of the creatine transport channel SLC6A8, a novel target that is enriched under hypoxic conditions and provides tumor cells with an additional energy source. Ompenaclid triggers tumor regressions in CRC patients by inducing apoptosis of tumor cells. The Phase 1b/2 study of ompenaclid in combination with FOLFIRI/BEV in second-line (2L) advanced or metastatic CRC patients has completed enrollment, with an ongoing follow up period. The primary endpoint of the study is to determine maximum tolerated dose (MTD), objective response rate (ORR), and treatment-emergent adverse events (TEAEs). In the dose escalation stage of the study, two dose levels of ompenaclid with FOLFIRI/BEV have been evaluated in patients with CRC with disease progression after a first-line oxaliplatin-containing regimen.

"There is a high unmet need for a safe and effective pan-RASm treatment in the advanced or metastatic CRC setting, and these data continue to show the potential of ompenaclid as a novel therapy that can improve upon the current standard-of-care," said Dr. Usman "Oz" Azam, M.D., Chief Executive Officer of Inspirna. "In addition to fully enrolling this Phase 1b/2 study, we are excited to announce that we have begun enrollment in a randomized controlled trial in the same indication and expect to have interim efficacy data in the second half of 2024."

Inspirna hosted a virtual KOL panel on Sunday, October 22, 2023, with Andrew Hendifar, M.D., to discuss these clinical data. The event replay may be accessed by registering at View Source

Key findings presented at ESMO (Free ESMO Whitepaper) Congress 2023:

As of September 18, 2023, 50 patients in the dose escalation/expansion cohorts received either 2400mg twice daily (BID) of ompenaclid plus FOLFIRI/BEV (n = 27) or 3000mg BID ompenaclid plus FOLFIRI/BEV (n = 23). 39 patients were evaluable for RECIST 1.1 response if they completed at least one treatment cycle and had at least one follow-up on treatment scan.
41 patients had RASm CRC.
ORR was 37% including 8 confirmed partial responses (PR) and 3 unconfirmed PRs (all 3 patients are ongoing) in the 30 evaluable patients.
Median progression-free survival (mPFS) was 10.2 months, and median overall survival (mOS) was 19.1 months across all 41 patients in the intention to treat population.
9 patients (all evaluable) had RAS-wildtype (RAS-wt) CRC.
ORR was 22%, including 1 confirmed PR and 1 unconfirmed PRs.
mPFS was 7.5 months and mOS was 14.5 months.
Across safety-evaluable patients (n = 48), ompenaclid was well-tolerated, and its safety profile in combination was similar to FOLFIRI/BEV alone, demonstrating its potential to be added to standard-of-care treatments.
The most common Grade ≤2 TEAEs were diarrhea (58%) and nausea (52%), frequent Grade ≥3 TEAEs were neutropenia (18%), diarrhea (13%), fatigue (10%) and abdominal pain (10%).
At both doses, systemic exposure was comparable and resulted in up to a 48x increase in urine creatine, suggesting robust SLC6A8 target inhibition.
No DLTs were observed in the dose escalation cohort, and MTD was not reached.
The abstract is published in the ESMO (Free ESMO Whitepaper) Congress 2023 Abstract Book, a supplement to the official ESMO (Free ESMO Whitepaper) journal, Annals of Oncology. The poster is available at the Annals of Oncology website and View Source

Poster Presentation Details

Title: Phase 1b/2 study of ompenaclid (RGX-202-01), a first-in-class oral inhibitor of the creatine transporter SLC6A8, in combination with FOLFIRI and bevacizumab (BEV) in RAS mutated (RASm) second-line (2L) advanced/metastatic colorectal cancer (mCRC)

Presenter: Andrew Hendifar, M.D., Assistant Professor of Medicine at Cedars-Sinai Medical Center and Study Principal Investigator

Onsite Poster Display Date: Sunday, October 22, 2023 at 9:00 AM CEST

Presentation Number: 646P

On October 23, 2023 Immunomic Therapeutics, Inc. (ITI), a privately-held clinical-stage biotechnology company pioneering the development of LAMP-mediated nucleic acid-based immunotherapy, reported safety and tolerability results from its phase 1 clinical trial evaluating ITI-3000, a plasmid DNA (pDNA) vaccine, targeting patients with Merkel cell carcinoma (MCC), a rare but aggressive form of skin cancer that is typically caused by the Merkel cell polyomavirus (MCPyV). ITI-3000 was granted Fast Track Designation (FTD) by the U.S. Food and Drug Administration (FDA) in November 2022 (Press release, Immunomic Therapeutics, OCT 23, 2023, View Source [SID1234636248]).

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"The reporting of results from our phase 1 trial of ITI-3000 in patients with MCC, marks the achievement of a significant milestone in our mission to create a therapeutic solution for this rare, yet highly aggressive skin cancer," stated D.G. Kim, Chief Executive Officer of ITI. "As we expected, ITI-3000 proved to be safe and well tolerated in the study, with no dose-limiting toxicities, no reported treatment-related adverse events or serious adverse reactions. As we are encouraged by the immunological responses in patients, we look forward to continuing the development of ITI-3000. The advancement of this program is paving the way for the expansion of our pipeline via our UNITE platform."

The phase 1 clinical trial was a six-patient, single center, open label, first-in-human (FIH) study, investigating the safety, tolerability and immunogenicity of ITI-3000 in patients with polyomavirus-positive Merkel cell carcinoma (MCC). Participants received 4 doses of ITI-3000 vaccine, one 4 mg dose every month for four months. Participants in the study were those who are both diagnosed and had completed standard of care (SOC) surgical and/or radiation therapy at least one year prior to enrollment in the study, and who had no evidence of active disease (NEAD). Participants who were previously diagnosed with MCC and had recurrence but exhibited no evidence of active disease (NEAD) for more than two years prior to enrollment, were also included in the study.

Additional information regarding the phase 1 trial may be found at clinicaltrials.gov, using identifier: NCT05422781.

About ITI-3000

ITI-3000 leverages the company’s investigational UNiversal Intracellular Targeted Expression (UNITE) platform, powered by LAMP (Lysosome Associated Membrane Protein), which fuses sequences from the mutated form of the large T antigen (LT) of the MCPyV into the sequence of the LAMP-1 gene. This lysosomal targeting technology has been shown to result in enhanced antigen presentation and a potent immune response.