On October 12, 2021 Kaleido Biosciences, Inc. (Nasdaq: KLDO), a clinical-stage biotech company with a differentiated, small-molecule approach to treating inflammatory conditions and diseases by selectively targeting the resident microbiome to restore gut-immune homeostasis, reported that CEO Dan Menichella will present a company overview at the Jefferies Virtual Next Generation IBD Therapeutics Summit at 1:45PM ET on Tuesday, October 19 (Press release, Kaleido Biosciences, OCT 12, 2021, View Source [SID1234591108]).

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The webcast of the presentation will be made available in the Investors & Media section of Kaleido’s website at View Source An archived replay will be available for 30 days following the event.

On October 12, 2021 Istari Oncology, Inc., a clinical-stage biotechnology company developing novel immunotherapies for the treatment of solid tumors, reported its first patient was dosed in the company’s LUMINOS-103 bladder cancer sub-study (NCT04690699) (Press release, Istari Oncology, OCT 12, 2021, View Source [SID1234591092]). In this sub-study, the safety and response to the company’s novel intratumoral viral immunotherapy, PVSRIPO, is being assessed as a neoadjuvant therapy with or without PD-1 inhibitors in adult bladder cancer patients who are ineligible for chemotherapy. Positive results from this sub-study may lead to a future trial to determine if radical cystectomy (removal of the bladder) could be avoided.

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PVSRIPO is an investigational immunotherapy based on the live–attenuated Sabin type 1 poliovirus vaccine that has been genetically modified for safety. PVSRIPO has been shown to activate a patient’s innate and adaptive immune system to facilitate a systemic anti-tumor immune response. Because PVSRIPO utilizes CD155 (the poliovirus receptor) to enter both solid tumor cells and antigen–presenting cells (APCs) in the tumor microenvironment, it has the potential to treat a variety of cancers.

"PVSRIPO has shown impressive responses with monotherapy in patients participating in two phase 1clinical trials focused on glioblastoma and melanoma," said Matt Stober, president and CEO at Istari Oncology. "We look forward to further evaluating its therapeutic value as we aim to expand the potential treatment options for patients living with bladder cancer."

LUMINOS-103 is a phase 1/2, multi-center, open-label, single-arm basket trial evaluating the administration of PVSRIPO with or without PD-1/L1 inhibitors across multiple tumor types, including muscle-invasive bladder cancer, and head and neck cancer (a sub-study that opened for enrollment in August 2021). The phase 2 LUMINOS-103 bladder cancer sub-study will be conducted at approximately 10 research sites across the U.S. It will evaluate both a neoadjuvant approach in patients with resectable disease, and separately in a cohort of patients with metastatic disease.

An analysis of each cohort comprising the LUMINOS-103 bladder cancer sub-study is planned once 25 to 30 patients per cohort have been enrolled and treated for at least two months. Study endpoints include objective response rate (by RECIST criteria), durability of response, progression and recurrence–free survival, and overall survival.

"Bladder cancer patients, particularly those who cannot receive cisplatin-based chemotherapy or who have advanced disease, are urgently in need of viable treatment options that limit systemic toxicity and improve patient outcomes," said Dr. Neal Shore, MD FACS, U.S. chief medical officer of surgery and urology at GenisisCare US and principal investigator responsible for dosing the first patient in Istari Oncology’s LUMINOS-103 bladder cancer sub-study. "We are excited to be initiating the LUMINOS-103 sub-study at the Carolina Urologic Research Center, and we are hopeful that the promising data achieved in previous clinical studies investigating PVSRIPO in patients with glioblastoma and melanoma will translate to positive outcomes for those in the bladder cancer community."

According to the Bladder Cancer Advocacy Network (BCAN), a national advocacy organization devoted to advancing bladder cancer research and supporting those impacted by the disease, bladder cancer most often begins in the urothelial cells that line the inside of the bladder with most tumors developing on the inner layer of the bladder. Bladder cancer becomes more difficult to treat as it grows through the layers of the bladder and into the muscle wall. Though less frequently, bladder cancer can also occur in the kidneys and ureters. The American Cancer Society estimates 84,000 new cases of bladder cancer in the U.S. in 2021.

For more information about Istari Oncology and its ongoing clinical trials, visit www.istarioncology.com.

About PVSRIPO
PVSRIPO is an investigational immunotherapy based on the live attenuated Sabin type 1 poliovirus vaccine that has been genetically modified for safety. PVSRIPO targets cells using the poliovirus receptor CD155, which is widely expressed on both the malignant cells of most solid tumors and key antigen presenting cells within the tumor microenvironment. PVSRIPO targets tumors using three key mechanisms: 1) engagement and activation of antigen presenting cells (APCs), leading to T cell priming and sustained, systemic anticancer immunity; 2) direct tumor cell killing and antigen release; and 3) amplification of the immune response via recall of poliovirus vaccine-specific T cells. PVSRIPO has been granted Breakthrough Therapy and Orphan Drug Designation status by the U.S. Food and Drug Administration in recurrent glioblastoma, and Fast Track and Orphan Drug Designation status in refractory melanoma.

On October 12, 2021 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported updated results from the Company’s ongoing Phase 1 CARBON trial evaluating the safety and efficacy of CTX110, its wholly-owned allogeneic CAR-T cell therapy targeting CD19+ B-cell malignancies (Press release, CRISPR Therapeutics, OCT 12, 2021, View Source [SID1234591138]).

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"We are excited to share positive data from our CARBON trial, which show that CTX110 could offer patients with large B-cell lymphomas an immediately available ‘off-the-shelf’ therapy with efficacy similar to autologous CAR-T and a differentiated safety profile," said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. "Furthermore, we have the potential to improve upon already observed efficacy with a consolidation dosing strategy. Based on these encouraging results, we are planning to expand CARBON into a potentially registrational trial in the first quarter of 2022."

CARBON Trial Overview
The Phase 1 CARBON trial is an open-label, multicenter clinical trial evaluating the safety and efficacy of CTX110 in adult patients with relapsed or refractory B-cell CD19+ malignancies who have received at least two prior lines of therapy. To date, enrollment has been focused on patients with the most aggressive disease presentations, including diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), high-grade double- or triple-hit lymphomas, and transformed follicular lymphoma. The majority of patients had Stage IV lymphoma and were refractory to their last line of therapy before entering the trial. Nine patients received prior autologous stem cell transplant. Patients who received prior autologous CAR-T therapy were not eligible.

As of the August 26, 2021 data cutoff, 30 patients with large B-cell lymphoma (LBCL) had been enrolled, of which 26 patients had received CTX110 with at least 28 days of follow-up and are included in the analysis. Only one enrolled patient did not receive CTX110. Three patients at the time of the data cut had less than 28 days of follow-up and were not evaluable for this analysis.

Patients were infused with a single CTX110 infusion following three days of a standard lymphodepletion regimen consisting of fludarabine (30mg/m2/day) and cyclophosphamide (500mg/m2/day). Patients could be re-dosed with CTX110 following disease progression. The primary endpoints include safety as measured by the incidence of dose limiting toxicities (DLTs) and overall response rate (ORR). Key secondary endpoints include complete response (CR) rate, duration of response and overall survival.

Additional details may be found at clinicaltrials.gov, using identifier: NCT04035434.

Safety
CTX110 was well tolerated across all dose levels. The adverse events of interest for all evaluable patients are shown in the table below.

There were no cases of Graft versus Host Disease (GvHD) and no infusion reactions to either lymphodepleting chemotherapy or CTX110.

All cases of cytokine release syndrome (CRS) were Grade 1 or 2 per the American Society for Transplantation and Cellular Therapy (ASTCT) criteria and either required no specific intervention or resolved following standard CRS management. Neither the frequency nor severity of CRS has increased in patients who were re-dosed with CTX110.

The only case of Grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS) was in the patient with concurrent HHV-6 encephalitis who was previously disclosed. There have been no cases of ICANS in any other patients treated at Dose Level (DL3) through Dose Level (DL4).

Only two patients experienced Grade 3 or higher infections: the previously discussed patient with HHV-6 encephalitis, and one patient who developed pseudomonal sepsis that resolved in four days.

Adverse events of interest N (%)

DL1 (N=3)

DL2 (N=3)

DL3 (N=6)

DL3.5 (N=6)

DL4 (N=8)

DL2+ (N=23)

Gr 1-2

Gr 3+

Gr 1-2

Gr 3+

Gr 1-2

Gr 3+

Gr 1-2

Gr 3+

Gr 1-2

Gr 3+

Gr 1-2

Gr 3+

CRS

1

–

2

–

2

–

3

–

6

–

13

–

(33)

(67)

(33)

(50)

(75)

(57)

ICANS

–

–

1

–

–

–

–

–

–

1

1

1

(33)

(13)

(4)

(4)

GvHD

–

–

–

–

–

–

–

–

–

–

–

–

Infusion reactions

–

–

–

–

–

–

–

–

–

–

–

–

Infections1

–

1

–

–

1

1

1

–

1

1

3

2

(33)

(17)

(17)

(17)

(13)

(13)

(13)

(9)

CRS and ICANS graded per ASTCT criteria; other adverse events graded per CTCAE; (1) All infections (bacterial, fungal, and viral) included

The emerging safety profile of CTX110 is positively differentiated from autologous CAR-T therapies that show high frequencies of severe CRS and ICANS, and from other allogeneic CAR-T therapies that require more toxic lymphodepletion regimens and can result in prolonged immunosuppression and increased risk of serious infections.

Clinical Activity
Data are shown below for the 26 patients that received CTX110 and had at least 28 days of follow-up. The ORR and CR rates for patients treated at DL2 and above are shown both on an intent-to-treat (ITT) and modified ITT (mITT) basis. ITT includes all enrolled patients (n=24 at DL2 and above) whereas mITT includes only those patients who received an infusion of CTX110 (n=23 at DL2 and above). Dose-dependent responses and durable complete responses were seen with CTX110. Disease assessment was performed by investigator review according to the 2014 Lugano response criteria.

Cell dose

DL1

DL2

DL3

DL3.5

DL4

DL2+ mITT

DL2+

(CAR+ T cells)

30×106

100×106

300×106

450×106

600×106

N=23

ITT

N=3

N=3

N=6

N=6

N=8

N=24

Overall response rate (ORR), N (%)

0 (0%)

1 (33%)

3 (50%)

4 (67%)

6 (75%)

14 (61%)

14 (58%)

Complete response (CR) rate, N (%)

0 (0%)

1 (33%)

2 (33%)

3 (50%)

3 (38%)

9 (39%)

9 (38%)

A single dose of CTX110 at DL2 and above resulted in a 58% ORR and 38% CR rate on an ITT basis.
Responses were seen in a variety of patients, including patients who had refractory disease, bulky disease, or who had progressed after prior autologous stem cell transplant.
The data demonstrate the potential for CTX110 to produce durable remissions, as evidenced by a 21% six-month CR rate (4 of the 9 patients who achieved CR at Day 28, remained in CR at 6 months; 5 patients had not reached their 6-month evaluation point), which is in the range of durable remissions observed with approved autologous CAR-T therapies on an ITT basis.
The data provide a strong rationale that consolidation dosing can improve on an already competitive profile for CTX110.
Based on this safety and efficacy profile, the Company plans to expand into a potential registrational trial that incorporates consolidation dosing in Q1 2022. In parallel, the Company continues to advance the rest of its immuno-oncology portfolio and scale its manufacturing capabilities in its new state-of-the-art manufacturing facility in Framingham, Massachusetts.

Conference Call and Webcast
To access the conference call, please dial +1 (866) 952-8559 (domestic) or +1 (785) 424-1743 (international) and reference the conference ID "CRISPR."

A live webcast of the event will be available on the "Events & Presentations" page in the Investors section of the Company’s website at View Source A webcast replay will be available on the CRISPR Therapeutics website after the event and will be archived for 14 days.

About CTX110
CTX110, a wholly owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting Cluster of Differentiation 19, or CD19. CTX110 is being investigated in the ongoing CARBON trial.

About CARBON
The ongoing Phase 1 single-arm, multi-center, open label clinical trial, CARBON, is designed to assess the safety and efficacy of several dose levels of CTX110 for the treatment of relapsed or refractory B-cell malignancies.

On October 12, 2021 Leidos (NYSE: LDOS), a FORTUNE 500 science and technology leader, reported that it has scheduled a conference call for Tuesday, Nov. 2, 2021, at 8 a.m. (ET) its third quarter financial results for the period ending Oct. 1, 2021 (Press release, Leidos, OCT 12, 2021, View Source [SID1234591093]). The company plans to issue its quarterly earnings press release before the conference call on Nov. 2, 2021.

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The details for the earnings conference call follow:

Replay:

A telephone playback of the third quarter earnings conference call is scheduled to be available beginning at 11:30 a.m. (ET) on Nov. 2, 2021, through 11:59 p.m. (ET) on Nov. 9, 2021. The replay will be accessible by calling 877-660-6853 (International callers: +1-201-612-7415), and entering conference ID 13723845.

An archived version of the webcast will be available on the Leidos Investor Relations website at View Source

On October 12, 2021 Sapience Therapeutics, Inc., a biotechnology company focused on the discovery and development of peptide therapeutics to address difficult to treat oncology indications, reported that it was awarded a Small Business Innovative Research (SBIR) grant from the National Cancer Institute (NCI) of the National Institutes of Health (NIH) to establish proof-of-concept for the use of its second clinical candidate, ST316, to treat Wnt/β-catenin-dependent breast cancer (Press release, Sapience Therapeutics, OCT 12, 2021, View Source [SID1234591110]).

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"The Wnt pathway has remained out of reach for traditional pharmaceutical approaches, and novel modalities like ST316 are urgently needed to provide new therapeutic options for cancer patients," said Jim Rotolo, Ph.D., VP, Translational Pharmacology and Head of Research of Sapience Therapeutics. "This grant from the NCI/NIH allows us to further characterize the in vitro activity and in vivo safety and activity of ST316, which will enable us to accelerate the advancement of this program toward the clinic."

Sapience CEO and President, Dr. Barry Kappel added, "With our ST316 program, we are addressing one of the most desired undruggable targets in cancer. ST316 was designed to disrupt the pathologic aspects of Wnt/β-catenin while leaving the physiologic activities of this important pathway intact, and we appreciate the NCI/NIH support of additional preclinical work to allow us to explore its full potential."

This grant was supported by the National Cancer Institute of the National Institutes of Health under Award Number R43CA265503. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About ST316
β-catenin is a critical member of the canonical Wnt signaling pathway, a well-known development stage pathway that has been considered an "undruggable" cancer target, as small molecules have proven ineffective or toxic. Wnt/β-catenin signaling drives cancer initiation and contributes to tumor growth, angiogenesis and metastasis. ST316 exerts its activity through disruption of the BCL9/β-Catenin interaction to suppress transcription of Wnt target genes regulating proliferation, migration, invasion, and the metastatic potential of tumor cells. Sapience anticipates advancing ST316 into IND-enabling studies in 2021 and initiating clinical studies in late 2022.