On January 18, 2022 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported that the Company will be presenting updated data from the DisTinGuish study, a Phase 2a clinical trial evaluating Leap’s anti-Dickkopf-1 (DKK1) antibody, DKN-01, in combination with tislelizumab, BeiGene’s anti-PD-1 antibody, in patients with gastric or gastroesophageal junction cancer (G/GEJ), at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal (GI) Cancers Symposium being held on January 20-22, 2022 (Press release, Leap Therapeutics, JAN 18, 2022, View Source [SID1234605541]).

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The Company will host a conference call with Dr. Samuel Klempner of Harvard Medical School and Massachusetts General Hospital on Friday, January 21, 2022 to discuss results from the study.

The latest results from Part A of the DisTinGuish study will be presented, representing first-line advanced G/GEJ patients treated with DKN-01 in combination with tislelizumab and chemotherapy. New data demonstrate compelling efficacy from this combination regimen, driven by enhanced clinical responses and survival benefit associated with high tumoral DKK1 expression that is independent of PD-L1 expression. Also to be presented are initial findings from the still-enrolling Part B of the clinical trial, studying DKN-01 and tislelizumab in second-line advanced G/GEJ patients with high tumoral DKK1 expression, showing the treatment is well tolerated with encouraging objective responses observed.

"The combination of DKN-01 with tislelizumab continues to demonstrate encouraging results in patients with gastric and gastroesophageal junction cancer, especially those in the DKK1-high subpopulation," said Samuel Klempner, MD, Associate Professor at Harvard Medical School who leads the gastric and esophageal cancer program at Massachusetts General Hospital Cancer Center and is a principal investigator on the DisTinGuish study. "The updated front-line results are encouraging in a difficult to treat cohort of primarily PD-L1 low patients, who are less likely to benefit from anti-PD-1 therapy. Together with encouraging initial findings from Part B, where DKN-01 and tislelizumab are used as a chemo-free second-line treatment of DKK1 high-expressing tumors, these results continue to support the therapeutic potential of DKN-01 and warrant exploration in a randomized clinical trial in first-line gastric and gastroesophageal junction patients."

About the DisTinGuish Study

The DisTinGuish study (NCT04363801) is a Phase 2a study of DKN-01 in combination with tislelizumab, an anti-PD-1 antibody, with or without chemotherapy as first-line or second-line therapy in patients with inoperable, locally advanced, G/GEJ adenocarcinoma. The study is being conducted in two parts in the United States and the Republic of Korea. Enrollment of Part A has been completed with 25 first-line HER2- G/GEJ cancer patients whose tumors express either high levels of DKK1 (DKK1-high) or low levels of DKK1 (DKK1-low). Part B of the study has enrolled 30 patients with second-line DKK1-high G/GEJ cancer and will continue to enroll up to 48 patients. Leap is conducting this combination study as part of an exclusive option and license agreement with BeiGene for the development of DKN-01 in Asia (excluding Japan), Australia, and New Zealand.

First-Line Part A Key Findings

· Overall preliminary median progression-free survival (PFS) was 10.7 months
o PFS was longer in DKK1-high patients at 11.9 months, compared to 10.7 months in DKK1-low patients
· Preliminary median duration of response (DoR) was 10.7 months in DKK1-high patients, compared to 7.9 months in DKK1-low patients
· Median overall survival has not been reached
· Among patients who received a full first cycle of DKN-01 (modified intent to treat, n=22), the objective response rate (ORR) was 68%, including one complete response (CR) and 14 partial responses (PR)
o 90% ORR in DKK1-high patients (n=10)
o 56% ORR in DKK1-low patients (n=9)
· Activity was independent of PD-L1 expression
o 79% ORR in PD-L1-low (vCPS < 5) and 67% ORR in PD-L1-high (vCPS > 5) patients
o 100% ORR in DKK1-high, PD-L1-low patients (n=6)
· Combination was well tolerated, safety profile consistent with previous update and reflecting the underlying patient population

Second-Line Part B Key Findings

· DKN-01 and tislelizumab administered in DKK1-high, PD-1 naïve patients was well tolerated at both 300mg and 600mg DKN-01 doses
· Among evaluable patients who received a full first cycle of DKN-01 (response evaluable modified intent to treat, n=20), the objective response rate (ORR) was 25%, including 5 PRs and 4 stable disease (SD). One additional patient has had an irPR by iRECIST criteria.
· PD-L1 expression is low overall in the study population and not correlated with DKK1 expression
· The study is ongoing and enrolling in the 600mg DKN-01 cohort. Twelve patients were on study at the time of the data cut, four of whom had not yet had their first imaging assessment.

Leap Presentation Details:

Title: DKN-01 and Tislelizumab ± Chemotherapy as a First-Line (1L) and Second-Line (2L) Investigational Therapy in Advanced Gastroesophageal Adenocarcinoma (GEA): DisTinGuish Trial

Session Type: Poster Session

Presenter: Samuel J. Klempner, Harvard Medical School

Date and Time: Thursday, January 20, 2022 at 3:00 p.m. Eastern Time

Conference Call

Leap will host a conference call on Friday, January 21, 2022 at 1:00 p.m. Eastern Time to further discuss the data. In addition to Leap’s executive management team, Dr. Samuel Klempner of Harvard Medical School and Massachusetts General Hospital will be on the call. The call can be accessed by dialing (866) 589-0108 (U.S. and Canada) or (409) 231-2048 (international). The passcode for the conference call is 3323348. The presentation will be webcast live and may be accessed on the Investors page of the Company’s website at View Source, where a replay of the event will also be available for a limited time.

About DKN-01

DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein. DKK1 modulates the Wnt/Beta-catenin and PI3kinase/AKT signaling pathways and has an important role in promoting tumor proliferation, metastasis, angiogenesis, and in mediating an immune suppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating NK cell ligands on tumor cells. The U.S. Food and Drug Administration has granted DKN-01 Orphan Drug Designation for the treatment of gastric and gastroesophageal junction cancer and Fast Track Designation in combination with tislelizumab for the treatment of patients with gastric and gastroesophageal junction adenocarcinoma whose tumors express high DKK1 protein, following disease progression on or after prior fluoropyrimidine- and platinum- containing chemotherapy and if appropriate, human epidermal receptor growth factor (HER2)/neu-targeted therapy.

On January 18, 2022 Lantern Pharma (NASDAQ: LTRN), a clinical stage biopharmaceutical company using its proprietary RADR artificial intelligence ("A.I.") platform to transform the cost, pace, and timeline of oncology drug discovery and development, reported a collaboration and research agreement with The Danish Cancer Society Research Center (DCRC) to support clinical development of Lantern’s acylfulvene class drug candidates, LP-100 and LP-184, as well as the development of improved diagnostic methods to identify nucleotide excision repair (NER) deficient tumors (Press release, Lantern Pharma, JAN 18, 2022, View Source [SID1234605540]). LP-100 and LP-184 have both shown synthetically lethal impact in tumors that are lacking NER capabilities. The DCRC is a cancer research institute within the Danish Cancer Society. The Danish Cancer Society is Denmark’s largest non-government organization and dedicates more than 60% of its budget to research, with the remainder shared between prevention and patient support initiatives. Lantern expects the data, genomic signatures and biological models generated from this collaboration to add millions of data points to RADR and help accelerate the development of new indications for LP-100 and LP-184. This collaboration, together with the growing power of the RADR platform, can potentially uncover new drug combinations using LP-100 and LP-184 for cancer treatments at a fraction of the cost of traditional drug development.

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The overall aim of the collaboration is to determine the most promising patient populations for future LP-100 (irofulven) and LP-184 therapy. The collaboration will focus on developing improved diagnostic tools to detect NER deficiency patient profiles more accurately. The research study conducted as part of the collaboration will use expanded mutational signature-based analyses to achieve this objective. The study will include a comprehensive analysis of breast, ovarian, prostate, lung, kidney, bladder, stomach, pancreatic and esophageal cancer. This collaboration will help determine how many patients and which patients can benefit for targeting NER deficiency and also help assess the overall market size for both LP-100 and LP-184 across multiple solid tumors.

"Inherent DNA repair deficiencies characterize a subset of many of our common tumor types and are increasingly relevant as markers of therapeutic responses. The focus on defining NER deficiencies as a potential marker for irofulven use is in line with our strategies on drug repurposing as well as personalized oncology," says Mef Nilbert, medical oncologist and research director at the DCRC.

The collaboration research will be led by Dr. Zoltan Szallasi, MD as principal investigator at DCRC. Dr. Szallasi serves joint appointments as Group Leader of the Translational Cancer Genomics department at DCRC and as Faculty, Computational Health Informatics Program (CHIP) and Assistant Professor of Pediatrics at Boston Children’s Hospital affiliated with Harvard Medical School.

"Through our breakthrough approach of collaborating with internationally recognized research centers such as DCRC, we are able to leverage and grow our proprietary RADR A.I. platform with millions of additional data points to further our ability to rapidly discover biomarker signatures aimed at helping identify patients more likely to respond to cancer therapies, which we believe will significantly reduce development timelines and cost of treatment," commented Panna Sharma, CEO and President of Lantern Pharma Inc. "We are assembling a growing body of data supporting LP-184 and LP-100’s synthetic lethality to tumor cells with either NER or HR deficiency, and our collaboration with DCRC will further accelerate our path to clinical trials as well as provide opportunities for new trials and additional targeted indications."

LP-184 is a DNA-damaging small molecule drug candidate currently in preclinical development for certain genomically defined solid tumors, including pancreatic cancer and glioblastoma. As a next-generation acylfulvene class agent that preferentially damages DNA in cancer cells overexpressing certain biomarkers, LP-184 has the potential to be used as both monotherapy as well as a synergistic agent in combination with other drugs. LP-184 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of malignant gliomas, as well as pancreatic cancer.

LP-100 exploits cancer cells’ deficiency in DNA repair mechanisms. LP-100 has the potential to be an important compound — either as monotherapy or in combination — for several challenging cancers that are impacting patients globally. LP-100 is in an existing genomic-signature guided phase 2 clinical trial in Denmark for patients with metastatic castration resistant prostate cancer (mCRPC). 9 patients (out of a targeted enrollment of 27) have been treated in the trial. The median overall survival (OS) for the initial group of 9 patients has been approximately 12.5 months, which is an improvement over other similar fourth-line treatment regimens for mCRPC.

On January 18, 2022 Kinnate Biopharma Inc. (Nasdaq: KNTE) ("Kinnate"), a biopharmaceutical company focused on the discovery and development of small molecule kinase inhibitors for difficult-to-treat, genomically defined cancers, reported that the U.S Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for KIN-3248, a next-generation pan-FGFR inhibitor being developed for intrahepatic cholangiocarcinoma (ICC) and urothelial carcinoma (UC)(Press release, Kinnate Biopharma, JAN 18, 2022, View Source [SID1234605539]).

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"The IND clearance for KIN-3248 is another important validation of our Kinnate Discovery Engine and an exciting step forward in our mission to deliver new therapies to patients with difficult-to-treat, genomically-defined cancers," said Nima Farzan, Chief Executive Officer of Kinnate. "By targeting clinically relevant primary FGFR driver alterations and secondary resistance mutations, including FGFR2 and FGFR3 gatekeeper, molecular brake, and activation loop mutations, we believe that KIN-3248 is unique among FGFR inhibitors and has the potential to extend the clinical response of cancer patients with FGFR-altered tumors."

KIN-3248 is an irreversible, small molecule pan-FGFR inhibitor that has been developed to address both primary FGFR2 and FGFR3 oncogenic alterations and those predicted to drive acquired resistance to current FGFR-targeted therapies, including gatekeeper, molecular brake, and activation loop mutations observed in cancers such as ICC and other gastrointestinal cancers. In preclinical studies, KIN-3248 demonstrated inhibitory activity across a wide range of clinically relevant mutations that drive primary disease and acquired resistance.

The Phase 1 trial is expected to initiate in the first half of 2022 and will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-cancer activity of KIN-3248 in FGFR inhibitor naïve and pretreated cancer patients with FGFR2 and/or FGFR3 gene alterations. The dose escalation portion (Part A) of the trial will determine the recommended dose and schedule of KIN-3248 for further evaluation in patients with FGFR2 and/or FGFR3 gene alterations. The dose expansion phase (Part B) of the trial will assess the safety and efficacy of KIN-3248 at the recommended dose and schedule in FGFR inhibitor naïve and pretreated patients with cancers driven by FGFR2 and/or FGFR3 gene alterations, including ICC, UC and other selected adult solid tumors.

Oncogenic FGFR (FGFR1, FGFR2, FGFR3, and FGFR4) gene alterations are observed in approximately 7% of all human cancers. FGFR2 gene fusions and FGFR3 activating alterations are predicted oncogenic drivers in approximately 10-20% of cholangiocarcinoma and 20-35% of urothelial cancers, respectively. While currently approved FGFR inhibitors and those in development provide clinical benefit in these cancer indications, disease progression typically occurs within 6-12 months of starting treatment and is often associated with the emergence of on-target resistance mutations within the FGFR kinase domain.

For more information about Kinnate’s pipeline of targeted oncology therapeutics, please visit: www.kinnate.com/science-and-pipeline.

On January 18, 2022 Incyte (Nasdaq:INCY) reported that it has scheduled its fourth quarter and year-end 2021 financial results conference call and webcast for 8:00 a.m. ET on Tuesday, February 8, 2022 (Press release, Incyte, JAN 18, 2022, View Source [SID1234605538]).

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The schedule for the press release and conference call/webcast is as follows:

• Q4 & YE 2021 Press Release:

February 8, 2022 at 7:00 a.m. ET

• Q4 & YE 2021 Conference Call:

February 8, 2022 at 8:00 a.m. ET

• Domestic Dial-In Number:

877-407-3042

• International Dial-In Number:

201-389-0864

• Conference ID Number:

13726298

If you are unable to participate, a replay of the conference call will be available for ninety days. The replay dial-in number for the U.S. is 877-660-6853 and the dial-in number for international callers is 201-612-7415. To access the replay you will need the conference ID number 13726298.

The live webcast with slides can be accessed at Investor.Incyte.com and will be available for replay for 90 days.

On January 18, 2022 ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, reported interim results (N=63) in its metastatic pancreatic cancer trial (QUILT 88) showing that the overall survival rate for patients doubled compared to historical survival rate of three months after two prior lines of therapy (Manax ASCO (Free ASCO Whitepaper) GI 2019) (Press release, ImmunityBio, JAN 18, 2022, View Source [SID1234605537]). The data of the Phase 2 trial studying a combination immunotherapy (Nant Cancer Vaccine) also show treatment-related serious adverse events were uncommon (8%) and no treatment-related deaths were reported. Based on these findings, ImmunityBio plans to meet with the FDA in 2022 to discuss the path for the approval of combination therapies for pancreatic cancer.

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The results were presented today at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal conference, which is being held virtually.

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States and has one of the highest mortality rates of all major cancers, taking nearly 50,000 lives in the U.S. every year. Surgery and subsequent adjuvant chemotherapy are the preferred treatment options for pancreatic cancer today, but the five-year survival rate for late-stage cases is just 3%. For the majority of patients who present with more advanced disease, treatment typically consists of chemotherapy alone or supportive care for metastatic patients, and chemotherapy with or without radiation for those with locally advanced disease, leaving patients seeking new options.

"There are thousands of patients in advanced stages of this disease and there are few, if any, treatment options for them," said Patrick Soon-Shiong, M.D., Founder and Global Chief Scientific and Medical Officer of ImmunityBio, Inc. "Based on this encouraging data from our QUILT 88 trial, we are hopeful that our Nant Cancer Vaccine can potentially address this unmet need. What’s more, we designed this therapeutic candidate to be administered in an outpatient setting making it more accessible to future patients than traditional immune checkpoint inhibitors."

To date, 27% of third-line or greater patients (17/63) remain on study. The median overall survival in this highly advanced group of patients, who failed two to six prior lines of treatment, is 5.8 months (95% CI: 3.9, 6.9 months) exceeding the approximately three-month historical median overall survival. Of the 63 patients, 30 (48%) had progressed after two prior lines of therapy. Median overall survival in this group was 6.3 months (95% CI: 5.0, 9.8 months), more than doubling the historical overall survival. On the strength of this early data and significant unmet medical need, the company has expanded enrollment in the third-line or greater cohort.

QUILT 88 is an open-label study to evaluate the safety and efficacy of the Nant Cancer Vaccine, comprising ImmunityBio’s IL-15 receptor agonist Anktiva (N-803), its off-the-shelf targeted natural killer cells (PD-L1 t-haNK), and aldoxorubicin, an albumin-modulated agent, plus low-dose chemotherapy. This combination Nant Cancer Vaccine is randomized against standard-of-care high-dose chemotherapy for first- and second-line treatment; the third-line or greater cohort, with an original target of 50 patients, is a single arm with the primary endpoint of overall survival.

QUILT-88 Study Details

This Phase 2, randomized, three-cohort, open-label study will evaluate the comparative efficacy and overall safety of standard-of-care chemotherapy versus low-dose chemotherapy in combination with PD-L1 t-haNK, Anktiva (N-803), and aldoxorubicin in subjects with locally advanced or metastatic pancreatic cancer (NCT04390399). Each treatment setting, as well as each first- and second-line or later maintenance treatment, will be evaluated independently as Cohorts A, B, and C, respectively, with Cohorts A and B having independent experimental and control arms. The study is expected to enroll 328 subjects across all three cohorts giving effect to the expanded enrollment of Cohort C (63 of 80 participants are currently enrolled in Cohort C, third-line or greater). The primary objective of Cohorts A and B is progression-free survival (PFS) per RECIST V1.1, and the objective of Cohort C is overall survival (OS). Secondary objectives include initial safety and additional efficacy measures, including overall response rate (ORR), complete response (CR) rate, durability of response (DoR), disease control rate (DCR), and overall survival (OS).

Currently, three trial sites have been activated: Hoag Memorial Hospital Presbyterian in Orange County, Calif., The Chan Soon-Shiong Institute for Medicine in Los Angeles County, Calif., and Avera McKennan Hospital and University Health Center in Sioux Falls, South Dakota, which serves patients in the tri-state area (Iowa, Nebraska and South Dakota).