On February 20, 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) reported that the loss of one copy of the miR15a/miR16-1 gene cluster promoted initiation and progression of multiple myeloma in mice, according to results published online in Blood Cancer Discovery, the latest journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, AACR (Free AACR Whitepaper), FEB 20, 2020, View Source [SID1234554626]).

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Multiple myeloma is a cancer of antibody-producing cells called plasma cells. It is preceded by a premalignant condition known as monoclonal gammopathy of undetermined significance (MGUS), in which abnormal plasma cells are present but do not expand. A hallmark of both MGUS and multiple myeloma is the detection of an M spike, which indicates the accumulation of an abnormal secreted antibody in the patient’s blood.

"The risk of progression from MGUS to malignant multiple myeloma is approximately 1 percent each year, but the factors that contribute to progression are not well understood," said Marta Chesi, PhD, associate professor of medicine at the Mayo Clinic. "The purpose of our study was to model genetic risk factors that may contribute to initiation and progression of multiple myeloma. This understanding could eventually allow us to identify the mechanisms that increase the risk of progressing to multiple myeloma."

One copy of chromosome 13 is deleted in approximately half of patients with MGUS and multiple myeloma; however, the significance of this deletion on prognosis and disease progression remains controversial. Chesi and colleagues hypothesized that individual genes on chromosome 13 may promote disease initiation and/or progression.

The authors examined the impact of two genetic loci found on human chromosome 13 – RB1 and MIR15A/MIR16-1 – on disease initiation and progression. Both RB1 and MIR15A/MIR16-1 are considered tumor suppressor genes due to their roles in regulating cellular proliferation. The RB1 protein is known to be inactivated in many cancers, including multiple myeloma. A previous study demonstrated that deletion of MIR15A/MIR16-1 enhances proliferation of human B cells, and deletion of the gene in mice promotes development of another blood cancer, chronic lymphocytic leukemia.

In this study, the authors deleted a single copy of either Rb1 or miR15a/miR16-1 in wild-type mice and in a transgenic mouse model of multiple myeloma they previously developed. The authors found that deletion of one copy of Rb1 did not affect disease initiation or progression. In contrast, deleting one copy of miR15a/miR16-1 in wild-type mice significantly accelerated the development of an M-spike. Furthermore, the deletion of one copy of miR15a/miR16-1 in mice with multiple myeloma significantly enhanced the aggressiveness of the disease and led to increased expression of genes that promote cellular proliferation.

The authors also analyzed a genetic dataset of multiple myeloma patients and found that deletion of one copy of MIR15A/MIR16-1 in patient tumors was associated with increased expression of the same cellular proliferation genes that were upregulated in mice.

"Losing one copy of the MIR15A/MIR16-1 gene appears to promote tumor cell proliferation in both mice and patients," said Chesi. "For many years, we thought that deletion of chromosome 13 was just a byproduct of other genetic changes in the tumor and that it did not directly affect disease progression. Our study now demonstrates that deletion of chromosome 13, and specifically deletion of MIR15A/MIR16-1, appears to alter the biology of the tumor.

"However, the fact that the entire chromosome 13, and not just MIR15A/MIR16-1, is lost in many cases of MGUS or multiple myeloma suggests that other genes on this chromosome are also likely to be important for pathogenesis," added Chesi. In particular, Chesi is interested in studying DIS3, another gene located on chromosome 13 that is frequently mutated in multiple myeloma. The authors were not able to assess its contribution in this study due to the lack of relevant mouse models.

Another limitation of the study is that it was not possible to delete Rb1 or miR15a/miR16-1 only in myeloma cells due to technical restrictions of their mouse model. As a result, these genes were deleted in all cells, including immune cells, which could have led to indirect effects on disease progression, explained Chesi. However, Chesi added that results from additional control experiments indicate that the observed results are unlikely to be indirect, as transplanted tumors behaved similarly in both wild-type and miR15a/miR16-1-deleted mice. This study was sponsored by grants from the National Institutes of Health. Chesi declares no conflict of interest.

On February 20, 2020 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted therapeutics for cancer and wet age-related macular degeneration through our license to Santen Pharmaceutical Co. Ltd., and utilizing our product development platform to partner with ex-U.S. companies to develop and commercialize innovative products in the U.S., reported that it will report its fourth quarter and full year 2019 financial and operating results after the close of U.S. financial markets on Thursday, February 27, 2020 (Press release, Tracon Pharmaceuticals, FEB 20, 2020, View Source [SID1234554615]). In addition, management will host a conference call to provide an update on corporate activities and discuss the quarterly and full year financial results.

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Conference call and webcast:
Date: February 27, 2020
Time: 4:30 pm Eastern Time (1:30 pm Pacific Time)
Dial-in: (855) 779-9066 (Domestic) or (631) 485-4859 (International)
Passcode: 3228345
Via web: www.traconpharma.com; "Events and Presentations" section within the "Investors" section
A replay of the webcast will be available for 60 days on the website.

On February 20, 2020 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported that Pascal Touchon, the Company’s President and Chief Executive Officer, will participate at two upcoming investor conferences in March (Press release, Atara Biotherapeutics, FEB 20, 2020, View Source [SID1234554614]):

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Cowen 40th Annual Health Care Conference
Fireside Chat: Monday, March 2, 2020 at 4:10 pm EST
Boston Marriott Copley Place in Boston, MA

Barclays Global Healthcare Conference
Company Presentation: Wednesday, March 11, 2020 at 11:45 am EDT
Loews Miami Beach Hotel in Miami Beach, FL

Live audio webcasts will be available by visiting the Investors & Media – News & Events section of atarabio.com. Archived replays of the webcasts will be available on the Company’s website for 14 days following the live webcasts.

On February 20, 2020 OPKO Health, Inc. (NASDAQ: OPK) reported that operating and financial results for the three months ended December 31, 2019, as well as provide guidance on expected revenues and operating expenses for the first quarter and full year 2020, after the close of the U.S. financial markets on Wednesday, February 26, 2020 (Press release, Opko Health, FEB 20, 2020, View Source [SID1234554613]).

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OPKO’s senior management will provide a business update and discuss its financial results in a live conference call and audio webcast beginning at 4:30 p.m. Eastern time on Wednesday, February 26, 2020.

CONFERENCE CALL & WEBCAST INFORMATION

OPKO’s senior management will provide a business update and discuss results in greater detail in a conference call and live audio webcast at 4:30 p.m. Eastern time on Wednesday, February 26, 2020. The conference call dial-in and webcast information is as follows:

DOMESTIC DIAL-IN: 877-783-8475
INTERNATIONAL DIAL-IN: 614-999-1827
PASSCODE: 9678678
WEBCAST: OPKO 4Q19 Results Conference Call

For those unable to participate in the live conference call or webcast, a replay will be available beginning approximately two hours after the close of the conference call. To access the replay, dial 855-859-2056 or 404-537-3406. The replay passcode is 9678678. The replay can be accessed for a period of time on OPKO’s website at OPKO 4Q19 Results Conference Call.

On February 20, 2020 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune diseases, reported interim data from its ongoing Phase II TACTI-002 study (Press release, Immutep, FEB 20, 2020, View Source [SID1234554592]). The results are being presented today at the 34th German Cancer Congress in Berlin by Principal Investigator, Dr. Bernhard Doger of START Madrid, Spain. The Company will also present this interim data and provide a further update on its clinical programs in a global webcast, details below.

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The data relates to use of the Company’s lead product candidate eftilagimod alpha ("efti" or "IMP321"), a soluble LAG-3 protein, as part of a combination treatment with pembrolizumab. The activation of antigen-presenting cells (APC) and subsequent T cell recruitment with efti may lead to stronger anti-tumour responses than observed with pembrolizumab alone.

Immutep CSO and CMO, Dr Frederic Triebel said: "The results we are seeing from our TACTI-002 trial are highly encouraging, with 47% of first line non-small cell lung cancer patients responding. These results are remarkable given that usually only 20% of patients respond to pembrolizumab monotherapy, if not pre-selected for high PD-L1 expression. Interestingly, patient responses are being seen in all three PD-L1 expression level groups, meaning the combination treatment seems to work even in patients not expected to respond to pembrolizumab monotherapy.

The initial overall response rate of 33% of second line head and neck squamous cell carcinoma patients is also very exciting, albeit from a smaller patient group. It compares well to an expected pembrolizumab monotherapy response rate of 15-18%, especially taking into account that three patients could not yet be assessed."

Immutep CEO, Marc Voigt stated: "We are very excited by the results from TACTI-002 as pembrolizumab monotherapy is approved only for PD-L1 subgroups in first line NSCLC. Seeing substantial response rates also in low PD-L1 expression groups from the combination therapy is very encouraging, particularly in light of the good safety profile to date for efti."

Immutep Limited, Level 12, 95 Pitt Street, Sydney NSW 2000

ABN: 90 009 237 889

Overview of the Trial

TACTI-002 is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada). It is evaluating the combination of efti with MSD’s KEYTRUDA (or pembrolizumab, an anti-PD-1 therapy) in up to 109 patients. All patients receive 200 mg of pembrolizumab every three weeks, along with 30 mg of efti every two weeks for the first eight cycles (1 cycle = 3 weeks) and every 3 weeks thereafter (starting cycle 9).

The trial is a Simon’s two-stage, open-label, single-arm study, with patients participating in three Parts:

Part A – First line Non-Small Cell Lung Cancer (NSCLC), PD-X naive

Part B – Second line NSCLC, PD-X refractory

Part C – Second line Head and Neck Squamous Cell Carcinoma (HNSCC), PD-X naive

TACTI-002 is an all comer study in terms of PD-L1 status, a well-known predictive marker for response to pembrolizumab monotherapy especially in NSCLC. PD-L1 expression is typically reported in three groups for NSCLC: < 1%, 1-49% and ³50% (Tumour Proportion Score or TPS). Patients with a high PD-L1 status are typically more responsive to anti-PD-1 monotherapy such as pembrolizumab, whereas those with low PD-L1 status are overall significantly less responsive. Pembrolizumab monotherapy is registered in the US and the EU for first-line NSCLC patients with a TPS score ³1% (US) and ³50% (EU), reflecting 65% and 30% of all first line NSCLC patients, respectively.

Key Findings

Stage 1 Part A (1st line NSCLC):

Overall Response Rate (ORR) of 47% and no patient with a response had progressive disease thus far

Distribution of the PD-L1 subgroups is as expected (see table) ~30% with ³ 50% PD-L1

Tumour responses are reported across all three PD-L1 expression level groups (< 1%, 1-49% and ³50%) for NSCLC. 5 out of the 8 responders had a PD-L1 expression <50%

Majority (10/17; 59%) of NSCLC patients are still under treatment and median PFS is not yet reached with all patients having passed the 7+ months mark already

PD-L1 status of stage 1 of Part A (n=17) are detailed below:

Immutep Limited, Level 12, 95 Pitt Street, Sydney NSW 2000

Interim ORR of 33% with 6 out of 18 patients reporting a response according to iRECIST (3 patients are not yet re-staged after initiation of therapy and PD-L1 results are currently being evaluated)

More detailed data will be provided as patient treatment duration advances.

Safety:

No new safety signals for this combination therapy reported thus far.

Recruitment Update

Recruitment is ongoing for stage 1 of Part B, along with stage 2 of Parts A and C. The table below summarises the number of patients recruited to date for the TACTI-002 cohorts.

The presentation entitled, ‘Initial results from a Phase II study (TACTI-002) in metastatic non-small cell lung or head and neck carcinoma patients receiving eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab’ will be made available on the Company’s website at View Source

Webcast Details

The Company will also present this interim TACTI-002 data and provide a further update on its clinical programs in a global webcast. The details for the webcast are as follows:

Date & Time:
Wednesday, February 26, 2020, 8:00 am Australian Eastern Daylight Time /

Tuesday, February 25, 2020, 4:00 pm US Eastern Daylight Time

Register:
Interested parties can register via a link to the webcast on the Company’s website or via the following link:

View Source

Questions: Investors are invited to submit questions in advance via [email protected].
A replay of the webcast will also be available at www.immutep.com from the day after the event.

About the TACT-002 trial

TACTI-002 (Two ACTive Immunotherapies) is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada). The study is evaluating the combination of efti with MSD’s KEYTRUDA (or pembrolizumab, an anti-PD-1 therapy) in up to 109 patients with second line head and neck squamous cell carcinoma or non-small cell lung cancer in first and second line. The trial is a Phase II, Simon’s two-stage, non-comparative, open-label, single-arm, multicentre clinical study that is taking place in up to 13 study centres across the U.S., Europe and Australia.