On December 13, 2021 Targovax ASA reported that its CEO, Erik Digman Wiklund, is invited to present at DNB’s Nordic Healthcare Conference (Press release, Targovax, DEC 13, 2021, View Source [SID1234596944]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

DNB’s 12th Nordic Healthcare Conference:
Date: 16 December 2021
Presenter: Erik Digman Wiklund (CEO)
Time: 09:50 CET

On December 13, 2021 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported updated positive data from the Phase 1 dose escalation portion of the AUGMENT-101 trial of SNDX-5613 in patients with mutant nucleophosmin (mNPM1) or mixed lineage leukemia rearranged (MLLr) relapsed/refractory (R/R) acute leukemias (Press release, Syndax, DEC 13, 2021, View Source [SID1234596942]). SNDX-5613 is the Company’s highly selective oral menin inhibitor . The data are being featured during an oral session at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on Monday, December 13, 2021 at 3:15 p.m. ET.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Patients with relapsed or refractory leukemia harboring NPM1 mutations or MLL-rearrangements face a particularly poor prognosis," said Eytan M. Stein, M.D., Assistant Attending Physician and Director, Program for Drug Development in Leukemia, Department of Medicine at Memorial Sloan Kettering Cancer Center, and the trial’s principal investigator. "Data being reported today show highly encouraging clinical activity and favorable tolerability across a heavily pretreated population. In addition to very high MRD negative rates in those patients achieving complete response (CR) or CR with partial hematologic recovery (CRh), we are also seeing response durations greater than six months."

"The updated data presented today at ASH (Free ASH Whitepaper) from our ongoing AUGMENT-101 trial strongly support the potential of SNDX-5613 to serve as a best-in-class treatment option for patients with NPM1 or MLLr leukemia, which together represents approximately 40% of all acute leukemias," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "We are also very pleased that discussions with the U.S. Food and Drug Administration (FDA) have confirmed that the ongoing Phase 2 AUGMENT-101 trial may potentially serve as the basis for regulatory filings in each of its three indication-specific cohorts of NPM1 mutant acute myeloid leukemia (AML), MLLr AML, and MLLr acute lymphoblastic leukemia (ALL), and that patients will be able to restart treatment with SNDX-5613 following a stem cell transplant."

Dr. Morrison continued, "We also remain focused on executing on our strategy to expand into earlier lines of therapy and pediatric populations, and we look forward to initiating the BEAT AML trial in frontline MLLr and mNPM1 AML in combination with venetoclax and azacitidine, the INTERCEPT trial in AML patients with MRD positive disease, and the AUGMENT-102 trial in combination with chemotherapy in adult and pediatric relapsed/refractory MLLr and mNPM1 acute leukemia patients."

As of an October 18, 2021 data cutoff date, a total of 59 patients with a median of four prior therapies, including 42% who received a prior stem cell transplant and 59% who received prior venetoclax, were dosed in the Phase 1 portion of the trial. Across evaluable patients with mNPM1 (n=13) or MLLr (n=38) acute leukemia who received at least one dose of SNDX-5613, the overall response rate1 (ORR) was 55%, with a CR/CRh rate of 24% and nine patients proceeding to stem cell transplant (two patients achieving a CR with incomplete platelet recovery [CRp] with no evidence of minimal residual disease [MRD], and seven patients who achieved MRD- CR or CRh). The ORR in evaluable patients harboring an NPM1 mutation was 38% (5/13), with a CR/CRh rate of 23% (3/13). The ORR in evaluable patients harboring an MLL-rearrangement was 61% (23/38), with a CR/CRh rate of 24% (9/38).

The overall MRD negative rate was 31% (16/51). Among those patients who achieved CR/CRh, 92% (11/12) were MRD negative, including 100% (3/3) of NPM1 patients and 89% (8/9) of MLLr patients. Median time to response for patients achieving a CR/CRh was two months. Median duration of response (DOR) was not reached, inclusive of patients who received stem cell transplant, and 6/12 patients who achieved CR/CRh had a duration of response greater than six months.

SNDX-5613 was well-tolerated, with no discontinuations due to treatment-related adverse events observed in heavily pretreated patients. The only dose limiting toxicity observed was Grade 3 QT prolongation, which occurred in 7% (3/43) of patients treated at the four doses that met the study’s pre-defined recommended Phase 2 dose criteria. Differentiation syndrome was reported in 14% of patients (8/59) with all cases being Grade 1 or 2 and readily managed with standard therapies.

As data from the Phase 1 portion of the trial have continued to mature, the results have demonstrated consistent and compelling anti-leukemic activity with favorable tolerability in patients with both R/R MLLr and NPM1 acute leukemias. The following table summarizes select efficacy and safety data that has been presented by the Company throughout 2021.

Best Response in Response Evaluable Patients

April ’21

May ’21

Dec ’21

n = 31 (%)

n = 31 (%)

n = 51 (%)

Overall Response Rate* (ORR)

15/31 (48%)

15/31 (48%)

28/51 (55%)

CR/CRh

5 (16%)

7 (23%)

12 (24%)

CRp

5 (16%)

4 (13%)

7 (14%)

CRi/MLFS

5 (16%)

4 (13%)

9 (18%)

Received HSCT

4

4

9

MLLr ORR

13/24 (54%)

13/24 (54%)

23/38 (61%)

mNPM1 ORR

2/7 (29%)

2/7 (29%)

5/13 (38%)

≥Gr3 QTc prolonged (all doses)

14%

14%

12%

≥Gr3 QTc prolonged (RP2D doses)

9%

9%

7%

* Overall Response Rate = CR + CRh + CRp + CRi + MLFS

The Phase 2 portion of AUGMENT-101, which will assess 163 mg every 12 hours of SNDX-5613 in patients receiving concomitant strong CYP3A4 inhibitor treatment, is currently underway. A total of 64 adult and up to ten pediatric patients will be enrolled across each of the following three distinct trial populations: patients with NPM1 mutant AML, patients with MLLr AML, and patients with MLLr ALL. Discussions with the FDA have confirmed that AUGMENT-101 may potentially serve as the basis for regulatory filings in each of the three distinct trials. The primary endpoint for each of the three trials will be efficacy as measured by complete remission rate (CR + CRh), with key secondary endpoints including DOR and overall survival.

A copy of today’s presentation will be available in the Publications and Meeting Presentations section of Syndax’s website.

About SNDX-5613

SNDX-5613 is a potent, selective, small molecule inhibitor of the menin-MLL binding interaction that is being developed for the treatment of mixed lineage leukemia rearranged (MLLr) acute leukemias including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), and NPM1 mutant AML. In preclinical models of MLLr acute leukemias, SNDX-5613 demonstrated robust, dose-dependent inhibition of tumor growth, resulting in a marked survival benefit. Menin-MLL interaction inhibitors have also demonstrated robust treatment benefit in multiple preclinical models of NPM1 mutant AML, which represents the most frequent genetic abnormality in adult AML. SNDX-5613 is currently being evaluated in the Company’s AUGMENT-101 Phase 1/2 open-label clinical trial for the treatment of relapsed/refractory (R/R) acute leukemias. SNDX-5613 was granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of patients with AML, and Fast Track designation for the treatment of adult and pediatric patients with relapsed or refractory acute leukemias harboring a mixed lineage leukemia rearranged MLLr or NPM1 mutation.

About Mixed Lineage Leukemia Rearranged Acute Leukemias

Rearrangements of the MLL gene give rise to mixed lineage leukemia rearranged (MLLr) acute leukemias known to have a poor prognosis, with less than 25% of adult patients surviving past five years. MLL rearrangements produce fusion proteins that require interaction with the protein called menin to drive leukemic cancer growth. Disruption of the menin-MLLr interaction has been shown to halt the growth of MLLr leukemic cells. MLLr leukemias, which are routinely diagnosed through currently available cytogenetic or molecular diagnostic techniques, occur in approximately 80% of infant acute leukemias and up to 10% of all acute leukemias. There are currently no approved therapies indicated for MLLr leukemias.

About NPM1 Mutant Acute Myeloid Leukemia

NPM1 mutant acute myeloid leukemia (AML), which is distinguished by point mutations in the NPM1 gene that drive the leukemic phenotype, is the most common type of cytogenetically normal adult AML and represents approximately 30% of all adult AML cases. This subtype of AML has a five-year overall survival rate of approximately 50%. Similar to mixed lineage leukemia rearranged (MLLr) leukemias, NPM1 mutant AML is highly dependent on the expression of specific developmental genes shown to be negatively impacted by inhibitors of the menin-MLL interaction. NPM1 mutant AML is routinely diagnosed through currently available screening techniques. There are currently no approved therapies indicated for NPM1 mutant AML.

On December 13, 2021 Sensei Biotherapeutics, Inc. (NASDAQ: SNSE), an immunotherapy company focused on the discovery and development of next generation therapeutics for cancer, reported it was added to the NASDAQ Biotechnology Index (NASDAQ: NBI), effective prior to market open on Monday, December 20, 2021 (Press release, Sensei Biotherapeutics, DEC 13, 2021, View Source [SID1234596938]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The NBI was launched in 1993 and includes securities of NASDAQ-listed companies that are classified according to the Industry Classification Benchmark as either biotechnology or pharmaceutical companies. Companies in the NBI must meet eligibility requirements, including average daily trading volume, minimum market capitalization, and other criteria. The index is evaluated annually in December and serves as the basis for the iShares NASDAQ Biotechnology Index Fund.

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).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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 Novo Nordisk reported that initiated a share repurchase programme in accordance with Article 5 of Regulation No 596/2014 of the European Parliament and Council of 16 April 2014 (MAR) and the Commission Delegated Regulation (EU) 2016/1052 of 8 March 2016 (the "Safe Harbour Rules") (Press release, Novo Nordisk, DEC 13, 2021, View Source [SID1234596934]). This programme is part of the overall share repurchase programme of up to DKK 20 billion to be executed during a 12- month period beginning 3 February 2021.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Under the programme initiated 5 November 2021, Novo Nordisk will repurchase B shares for an amount up to DKK 3.7 billion in the period from 11 November 2021 to 1 February 2022.

Since the announcement 6 December 2021, the following transactions have been made:

The details for each transaction made under the share repurchase programme are published on novonordisk.com.

With the transactions stated above, Novo Nordisk owns a total of 30,415,276 B shares of DKK 0.20 as treasury shares, corresponding to 1.3% of the share capital. The total amount of A and B shares in the company is 2,310,000,000 including treasury shares.

Novo Nordisk expects to repurchase B shares for an amount up to DKK 20 billion during a 12- month period beginning 3 February 2021. As of 10 December 2021, Novo Nordisk has since 3 February 2021 repurchased a total of 31,661,725 B shares at an average share price of DKK 565.96 per B share equal to a transaction value of DKK 17,919,256,493.