On June 7, 2021 Citius Pharmaceuticals, Inc. ("Citius" or the "Company") (Nasdaq: CTXR), a biopharmaceutical company dedicated to the development and commercialization of first-in-class critical care products with a focus on anti-infective products in adjunct cancer care, unique prescription products and stem cell therapy, reported that it is set to be added to the Russell 2000 Index at the conclusion of the Russell US Indexes annual reconstitution, effective at the opening of the U.S. equity markets on June 28, 2021 (Press release, Citius Pharmaceuticals, JUN 7, 2021, View Source [SID1234583683]).

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"Our inclusion in the Russell index is an important milestone for Citius that reflects the continued progress we are making to develop and commercialize first-in-class treatment options for patients around the world. We welcome the enhanced visibility of our diversified pipeline and long-term growth potential, and look forward to sharing our future milestones with a broader investment community," said Myron Holubiak, President and Chief Executive Officer of Citius.

FTSE Russell determines membership for its Russell indexes primarily by objective, market-capitalization rankings and style attributes. Membership in the small-cap Russell 2000 Index, which remains in place for one year, is based on membership in the broad-market Russell 3000Ò Index. Citius stock will also be automatically added to the appropriate growth and value indexes.

Russell indexes are widely used by investment managers and institutional investors for index funds and as benchmarks for active investment strategies. Approximately $9 trillion in assets are benchmarked against Russell’s US indexes. Russell indexes are part of FTSE Russell, a leading global index provider.

For more information on the Russell 2000 Index and the Russell indexes reconstitution, visit the FTSE Russell website.

On June 7, 2021 Linnaeus Therapeutics, Inc. (Linnaeus), a privately held clinical-stage biopharmaceutical company focused on the development and commercialization of novel small-molecule oncology therapeutics, reported the presentation of clinical data from its phase 1 dose-escalation study of LNS8801 as a monotherapy and in combination with pembrolizumab at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, Linnaeus Therapeutics, JUN 7, 2021, View Source [SID1234583682]).

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The poster was entitled, "Phase 1 trial of a novel, first-in-class G protein-coupled estrogen receptor (GPER) agonist, LNS8801, in patients with advanced or recurrent treatment-refractory solid malignancies."

In the phase 1 dose-escalation portion of the study, LNS8801 demonstrated exceptional safety and tolerability. With monotherapy, no dose-limiting toxicities (DLTs) or treatment-related serious adverse events were observed. The combination of LNS8801 and pembrolizumab was confirmed to be safe and tolerable with no DLTs observed. The recommended phase 2 dose (RP2D) of LNS8801 dosed alone or in combination with pembrolizumab has been identified as 125 mg daily.

Putative predictive, prognostic, and confirmatory biomarkers that correlate well with anticancer activity and clinical benefit have been identified. These biomarkers will aid in the selection of patients in future clinical studies and will continue to be validated in the phase 2a program.

During dose escalation, LNS8801 demonstrated provocative signals of monotherapy and combinatorial activity in multiple settings of high unmet medical need. With LNS8801 monotherapy, 32% of all patients and 78% of biomarker-identified patients dosed at or above the RP2D had disease control and stable disease by RECIST 1.1. In immune-checkpoint inhibitor intolerant cutaneous melanoma, significant reductions in tumor size and ongoing/prolonged disease control (62+ weeks) have been observed in 2 of 2 patients. In metastatic uveal melanoma, 80% of patients dosed at or above the RP2D had stable disease (26+ weeks). In combination with pembrolizumab, a 33% objective response rate and a 100% disease control rate were observed (n=3), including a partial response in a pembrolizumab-experienced non-small cell lung cancer patient.

"We are extremely pleased to showcase these data at ASCO (Free ASCO Whitepaper)," commented Patrick Mooney, MD, CEO of Linnaeus. "The data from the phase 1 study clearly demonstrate that LNS8801 is extremely safe and well tolerated and shows very promising signs of clinical benefit and preliminary efficacy alone and in combination with pembrolizumab. We look forward to further exploring LNS8801 alone and in combination with pembrolizumab in the currently open phase 1b cohorts and when we soon open additional phase 2a expansion cohorts."

Having completed the dose-escalation phase of the study, Linnaeus is currently testing LNS8801 in its phase 1/2a adaptive-design clinical trial as a monotherapy and in combination with KEYTRUDA (pembrolizumab) in patients who had previous clinical benefit from immune checkpoint inhibitors and then subsequently progressed. This marks the first time any company has dosed a patient in a clinical trial specifically targeting the GPER in combination with pembrolizumab. Linnaeus is also evaluating LNS8801 in a monotherapy cohort in patients with metastatic cutaneous melanoma who are PD-1/L1 therapy intolerant.

Linnaeus intends to open phase 2a cohorts in the near term.

About LNS8801
LNS8801 is an orally bioavailable and highly specific and potent agonist of GPER whose activity is dependent on the expression of GPER. GPER activation by LNS8801 rapidly and durably depletes c-Myc protein levels. In preclinical cancer models, LNS8801 displays potent antitumor activities across a wide range of tumor types, rapidly shrinking tumors and inducing immune memory.

In the ongoing phase 1/2a study in humans, LNS8801 monotherapy has been safe and well tolerated. Additionally, LNS8801 has demonstrated target engagement, c-Myc protein depletion, and clinical benefit in patients with advanced cancer.

On June 7, 2021 Therapeutic Solutions International, Inc., (OTC Markets: TSOI), reported potent synergy between its tumor blood vessel targeting StemVacs-V iPSC immunotherapy and several classical tumor specific therapeutic vaccines (Press release, Therapeutics Solutions International, JUN 7, 2021, View Source [SID1234583681]).

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In a series of experiments tumor growth administration of dead tumor cells together with StemVacs-V resulted in potent immunological memory to the tumor cells, which could be transferred to immunologically naïve mice. Additionally, the experiments demonstrated killing tumor cells using conventional approaches such as chemotherapy, when performed together with StemVacs-V iPSC, led to the development of immunological memory towards the specific cancer.

"By targeting the blood vessels that feed the cancer, StemVacs-V iPSC causes enhanced necrotic cell death, which stimulates systemic immunity against the cancer throughout the whole body," said Dr. James Veltmeyer, Chief Medical Officer of the Company. "We are extremely enthusiastic by the current data showing that our blood vessel targeting approach can be used to synergize with both cancer immunotherapies and non-immune therapies of cancer such as chemotherapy and radiation therapy."

Despite cancer immunotherapy being an over 100 billion dollar a year market in 2020, most cancers still do not respond to this approach. These are called "cold tumors." It is believed that by starving the cancer of its blood supply, StemVacs-V iPSC may convert cold tumors to immunotherapy sensitive "hot tumors."

"The potential implications of the current data, which is covered by our previously filed patents, include synergies with oncolytic viruses, checkpoint inhibitors, fractionated radiation therapy, antibodies, and chemotherapies," said Famela Ramos, Vice President of Business Development for Therapeutic Solutions International. "We are currently exploring numerous co-development partnerships."

"This new finding is extremely exciting because it opens the door to synergies with other immunotherapies such as CAR-T therapies, which although successful in liquid tumors, to date have not yielded promising results in solid and/or cold tumors," said Timothy Dixon, President and CEO of the Company. "Having SAB members such as Santosh Kesari and Francesco Marincola, who are at the forefront of cancer immunotherapy, significantly positions us to accelerate the development of our new approach which targets the "Achille’s Heel of cancer."

On June 7, 2021 Bausch Health Companies Inc. (NYSE/TSX: BHC) ("Bausch Health," the "Company" or the "Offeror") reported the results to date of its pending cash tender offer (the "Tender Offer"), to purchase any and all of its outstanding 7.00% Senior Secured Notes due 2024 (the "Notes"), as well as the anticipated early settlement date for the Tender Offer on June 8, 2021 (the "Early Settlement Date") (Press release, Bausch Health, JUN 7, 2021, View Source [SID1234583680]).

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The terms and conditions of the Tender Offer are described in an Offer to Purchase dated May 24, 2021 (as it may be amended or supplemented from time to time, the "Offer to Purchase"). All terms and conditions of the Tender Offer remain unchanged as set forth in the Offer to Purchase.

As of 5:00 p.m., New York City time, on June 7, 2021 (the "Early Tender Date"), the aggregate principal amount of Notes validly tendered and not validly withdrawn is $545,079,000. The Offeror expects to accept for purchase all of the Notes validly tendered prior to the Early Tender Date, subject to the satisfaction of the conditions to such Tender Offer. The Offeror expects that the conditions to the Tender Offer will be satisfied as of the Early Settlement Date.

The total consideration for each $1,000 principal amount of Notes is $1,019.25 plus accrued and unpaid interest (the "Total Consideration") and is expected to be paid on the Early Settlement Date to the holders of Notes tendered and accepted for purchase as of the Early Tender Date. The Total Consideration includes an early tender premium of $30.00 per $1,000 principal amount of Notes accepted for purchase as of the Early Tender Date. In addition to the Total Consideration, all Holders of Notes accepted for purchase pursuant to the Tender Offer will also receive accrued and unpaid interest on the Notes from the last interest payment date to, but not including, the Early Settlement Date.

The Tender Offer remains open and will expire at 11:59 p.m., New York City time, on June 21, 2021 (such date and time, as it may be extended, the "Expiration Date"). No tenders will be valid if submitted after the Expiration Date. The Offeror expects to purchase any remaining Notes tendered following the Early Settlement Date that have been validly tendered at or prior to the Expiration Date and accepted for purchase, subject to all conditions to the Tender Offer having been either satisfied or waived by the Offeror, promptly following the Expiration Date (the date of such acceptance and purchase, the "Final Settlement Date"). The Final Settlement Date is expected to occur on the second business day following the Expiration Date, assuming the conditions to the Tender Offer and the Solicitation have been either satisfied or waived by the Offeror at or prior to the Expiration Date and all of the outstanding Notes are not purchased on the Early Settlement Date.

The Tender Offer is subject to, and conditioned upon, the satisfaction or waiver of certain conditions described in the Offer to Purchase, including the completion of the Company’s previously announced private offering of $1.6 billion aggregate principal amount senior secured notes, on terms acceptable to the Company.

The deadline for holders to validly withdraw tenders of Notes has passed. Accordingly, Notes that were already tendered at the Early Tender Date and any additional Notes that are tendered at or prior to the Expiration Date may not be withdrawn, except in certain limited circumstances where additional withdrawal rights are required by law.

If, following the consummation of the Tender Offer, any Notes remain outstanding, the Offeror intends to redeem such Notes in accordance with terms of the Notes and the indenture, dated as of March 21, 2017 (as amended or supplemented), among Bausch Health, the subsidiaries signatory thereto, The Bank of New York Mellon, as trustee, and the notes collateral agents party thereto under which the Notes were issued.

Goldman Sachs & Co. LLC is acting as the dealer manager in the Tender Offer. Global Bondholder Services Corporation has been retained to serve as both the depositary and the information agent for the Tender Offer. Persons with questions regarding the Tender Offer should contact Goldman Sachs & Co. LLC at (collect) (212) 902-5962 or (toll free) (800) 828-3182. Requests for copies of the Offer to Purchase and other related materials should be directed to Global Bondholder Services Corporation at (toll-free) (866) 470-3800 or (collect) (212) 430-3774.

None of the Offeror, its board of directors or officers, the dealer manager, the depositary, the information agent or the trustee with respect to the Notes, or any of their respective affiliates, makes any recommendation that holders tender or refrain from tendering all or any portion of the principal amount of their Notes, and no one has been authorized by any of them to make such a recommendation. Holders must make their own decision as to whether to tender their Notes and, if so, the principal amount of Notes to tender. The Tender Offer is made only by the Offer to Purchase. This news release is neither an offer to purchase nor a solicitation of an offer to sell any notes in the Tender Offer. The Tender Offer is not being made to holders of Notes in any jurisdiction in which the making or acceptance thereof would not be in compliance with the securities, blue sky or other laws of such jurisdiction. In any jurisdiction in which the Tender Offer is required to be made by a licensed broker or dealer, the Tender Offer will be deemed to be made on behalf of the Offeror by the dealer manager or one or more registered brokers or dealers that are licensed under the laws of such jurisdiction.

Any securities issued pursuant to the financing transactions described above will not be registered under the Securities Act of 1933, as amended (the "Securities Act"), or any state securities law and may not be offered or sold in the United States absent registration or an applicable exemption from registration under the Securities Act and applicable state securities laws. Such securities have not been and will not be qualified for sale to the public by prospectus under applicable Canadian securities laws and, accordingly, any offer and sale of the securities in Canada will be made on a basis which is exempt from the prospectus requirements of such securities laws.

On June 7, 2021 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported in an oral presentation at the 57th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, updated results from a Phase II study of the MDM2-p53 inhibitor alrizomadlin (APG-115) in combination with pembrolizumab in patients with unresectable or metastatic melanoma or advanced solid tumors that have progressed on prior immuno-oncologic (IO) drugs (Press release, Ascentage Pharma, JUN 7, 2021, View Source;ascentage-pharma-presents-updated-results-of-mdm2-p53-inhibitor-alrizomadlin-apg-115-demonstrating-an-orr-of-24-1-including-complete-response-in-combination-with-pembrolizumab-in-patients-with-advanced-mel-301307261.html [SID1234583679]).

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As a leading Chinese biotechnology company with progressive visibility at international scientific congresses in recent years, Ascentage Pharma’s clinical study results have been selected for presentations at the ASCO (Free ASCO Whitepaper) Annual Meeting for the fourth year. This year, results from four of its studies clinical studies were selected for presentations at the meeting, including two oral presentations. The clinical study data from the on-going Phase II study of alrizomadlin have demonstrated a manageable safety profile and meaningful clinical antitumor activity, including one patient with a complete response (CR), an objective response rate (ORR) of 24.1% and a disease control rate (DCR) of 55.2% in the PD-1/PD-L1 inhibitor-resistant melanoma cohort. In addition, partial responses (PRs) were reported in enrolled patients with other tumor types.

"The clinical data of alrizomadlin presented in our oral presentation are encouraging, as they suggest clinical activity in hard-to-treat tumor types across multiple indications, including several without currently available standard of care, such as relapsed or refractory melanoma subtypes," said Dr. Anthony W. Tolcher, Founder and CEO of NEXT Oncology, Director of Clinical Research at Texas Oncology, and the Global Principal Investigator of the study. "Our data provide a clinical validation of the recently published paper in Nature Immunology demonstrating that alrizomadlin synergizes with immunotherapy by sustaining STAT5 stability and controlling T-cell-mediated antitumor immunity via the novel pathway of MDM2 inhibition. This seminal publication elucidates why patients who previously failed to respond to IO therapy may derive clinical benefit from the addition of alrizomadlin to the IO agent pembrolizumab."

"This study of alrizomadlin in combination with pembrolizumab offers a clinical validation of the therapeutic synergy between MDM2-p53 inhibitors and existing immuno-oncologic drugs and shows the potential as a new treatment option that could bring renewed hope for patients with solid tumors," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "At this year’s ASCO (Free ASCO Whitepaper) Annual Meeting, we have announced results from multiple studies, including that of Alrizomadlin, in two oral presentations and two poster presentations. I am very proud of these advances, which attest to Ascentage Pharma’s robust capabilities in global innovation. Moving forward, we will remain committed to our mission of addressing unmet clinical needs in China and around the world, and strive to accelerate our clinical programs in the hope of soon benefitting patients."

An overview of the four abstracts presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting:

Drug Candidate

Abstract Title

Abstract #

Format

Lisaftoclax

(APG-2575)

First-in-human study of lisaftoclax (APG-2575), a novel Bcl-2 inhibitor (Bcl-2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs)

7502

Oral

Presentation

Alrizomadlin

(APG-115)

Preliminary results of a phase II study of alrizomadlin (APG-115), a novel, small-molecule MDM2 inhibitor, in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (I-O) drugs

2506

Oral

Presentation

Trial in progress: A phase I/II trial of novel MDM2 inhibitor alrizomadlin (APG-115), with or without platinum chemotherapy, in patients with p53 wild-type salivary gland carcinoma

TPS6094

Poster

Presentation

Pelcitoclax

(APG-1252)

Trial in progress: A multicenter phase Ib/II study of pelcitoclax (APG-1252) in combination with paclitaxel in patients with relapsed/refractory small-cell lung cancer (R/R SCLC)

TPS8589

Poster

Presentation

Highlights of the oral presentation on alrizomadlin at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting:

Preliminary results of a phase II study of alrizomadlin (APG-115), a novel, small-molecule MDM2 inhibitor, in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (I-O) drugs

Abstract: #2506

This open-label, multicenter Phase II study in the US assessed the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of alrizomadlin in combination with pembrolizumab in patients with advanced solid tumors.
As of April 15, 2021, 102 patients had been enrolled in the Phase II part of the study and treated with alrizomadlin at the recommended Phase II dose (RP2D) of 150 mg every other day, in combination with pembrolizumab. This study has 6 cohorts, including patients with: PD-1/PD-L1 inhibitor-resistant melanoma, non-small cell lung cancer (NSCLC), and urothelial carcinoma; or malignant peripheral nerve sheath tumor (MPNST), liposarcoma, and ATM mutant solid tumors.
Antitumor Effects:
In the PD-1/PD-L1 inhibitor-resistant melanoma cohort (n=29), there was 1 confirmed partial response (PR) out of 7 patients with uveal (ocular) melanoma; 2 PRs (1 confirmed + 1 unconfirmed) out of 5 patients with mucosal melanoma; and 1 complete response (CR, confirmed) and 3 PRs (2 confirmed + 1 unconfirmed) out of 15 patients with cutaneous melanoma. The ORR and DCR in the melanoma cohort were 24.1% (7/29) and 55.2% (16/29), respectively.
In the MPNST cohort (n=6), 1 PR (unconfirmed).
In the liposarcoma cohort (n=16), 1 PR (unconfirmed) and 12 stable diseases (SDs), at a DCR of 81.2% (13/16).
In the PD-1/PD-L1 inhibitor-resistant NSCLC (n=15) and urothelial carcinoma (n=8 evaluable) cohorts, 1 patient in each cohort achieved confirmed PR.
Common treatment-related adverse events (TRAEs) observed in more than 10% of patients were nausea, thrombocytopenia, vomiting, fatigue, decreased appetite, diarrhea, neutropenia, and anemia.
In conclusion, alrizomadlin combined with pembrolizumab is well tolerated, and did not exhibit any overlapping toxicity. These preliminary results have established proof of concept clinically that the combination regimen has antitumor activity in patients with IO relapsed/refractory metastatic melanoma, (including uveal melanoma, mucosal melanoma, or cutaneous melanoma). In addition, this combination therapy also showed promising antitumor activity in patients with MPNST or liposarcoma for which pembrolizumab has no approved indications.