On December 15, 2021 Alligator Bioscience AB ("Alligator") and Aptevo Therapeutics ("Aptevo") (NASDAQ: APVO) reported publication of an article in the December 15, 2021, issue of the peer-reviewed journal, Nature Communications on the mechanism of action of CD137 (4-1BB) targeting bispecific antibodies (Press release, Alligator Bioscience, DEC 15, 2021, View Source [SID1234597187]). Nature Communications is an open access, multidisciplinary journal dedicated to publishing high-quality research in all areas of the biological, health, physical, chemical and Earth sciences.

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The article titled, CD137 (4-1BB) co-stimulation of CD8 T cells is more potent when provided in cis than in trans with respect to CD3-TCR stimulation, details the mechanism of action of 4-1BB targeting bispecific antibodies. This work was published in collaboration by internationally renowned 4-1BB expert, Professor Ignacio Melero, and his team at the University of Navarra, Pamplona, Spain. Professor Melero’s data supports the bispecific antibodies, such as ALG.APV-527, targeting 4-1BB, and link 4-1BB signaling in cis (directly to tumor targets, such as 5T4), are more efficient at stimulating the anti-tumor response than bispecific agents that link 4-1BB signaling in trans to adjacent non-tumor cell targets such as the stroma.

"This study unveils an important mechanism for tumor-cell targeting therapies for cancer. Bispecific antibodies targeting 4-1BB offer a synthetic biology that can be very useful in cancer immunotherapy. In this study, we found a spatial requirement in regard to antigen recognition and 4-1BB co-stimulation. This means that the T cells can detect the antigen on the same cell that is providing natural or artificial 4-1BB co-stimulation. This type of co-stimulation, and the ensuing immune system activation and survival, is far more potent. The bispecific antibody from Alligator Bioscience and Aptevo Therapeutics, ALG.APV-527, is a tool that shows this potent 4-1BB co-stimulation in the tumor microenvironment and has the potential to provide a superior therapy to treat cancers," stated Ignacio Melero, MD, PhD, Cima and Clínica Universidad de Navarra, Spain.

"We are very pleased to have been selected for publication in a high-ranking peer-reviewed journal such as Nature Communications. This is very encouraging and validates the superior mechanism and design of ALG.APV-527. The data further highlights the strong positioning of ALG.APV-527 in the bispecific 4-1BB antibody field," said Søren Bregenholt, CEO at Alligator.

"The publication of Professor Melero’s findings further support the potential of ALG.APV-527 overall, to evoke an effective tumor-targeting immune response with fewer adverse events. This work highlights the potential differentiating benefit of ALG.APV-527 to induce stronger and more tumor-directed T cell responses with the potential for improved safety and efficacy in patients and represents a significant contribution from the scientific teams at Aptevo and Alligator. We are proud of their achievements and know their work will continue producing invaluable data going forward," commented Marvin White, CEO of Aptevo.

The complete article is available in print and in digital format which can be viewed via the following link: (link to article).

About ALG.APV-527

ALG.APV-527 is a 4-1BB and tumor-binding immunomodulatory antibody. 4- 1BB has the ability to stimulate the immune cells (anti-tumor specific T cells) involved in tumor control, making 4-1BB a particularly compelling target for cancer immunotherapy. The tumor-binding part of ALG.APV-527 targets the 5T4 tumor-associated antigen. 5T4 is a protein expressed in multiple tumor types, as well as certain types of aggressive tumor cells (tumor-initiating cells), but at low levels or not at all in normal tissue, making 5T4 a compelling target molecule for cancer therapy.

Alligator and Aptevo are advancing ALG.APV-527 into Phase I clinical development. The companies will continue to explore licensing opportunities as ALG.APV-527 moves into clinical development.

On December 15, 2021 Sareum Holdings plc (AIM: SAR), the specialist drug development company delivering targeted small molecule therapeutics to improve the treatment of cancer and autoimmune diseases, reported that the European Patent Office has issued an Intention to Grant notice for a patent in respect of an invention associated with Sareum’s proprietary SDC-1802 TYK2/JAK1 Kinase Inhibitor Programme (Press release, Sareum, DEC 15, 2021, View Source [SID1234597211]).

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The patent (EPO Patent Application no. 17787186.0) will protect the SDC-1802 molecule and pharmaceutical preparations thereof as a therapeutic to treat TYK2-dependent T-cell acute lymphoblastic leukaemia (T-ALL – a cancer of a particular type of white blood cell called a T lymphocyte) by inhibiting TYK2 kinase. This programme is in preclinical development.

The Company expects that the patent will be formally granted within four months, subject to certain formalities being completed.

Sareum’s CSO, Dr John Reader, commented:

"Our aim is to build broad robust patent protection for our proprietary TYK2/JAK1 inhibitor candidates as they advance through their respective development programmes, to ensure that Sareum retains full value in these programmes as part of its business development discussions. We are pleased therefore to receive this ‘Intention to Grant’ notice from EPO around our patent application for SDC-1802 as a potential treatment for T-ALL. We expect to complete the formalities that would lead to a full grant of this patent in due course."

On December 15, 2021 Perimeter Medical Imaging AI, Inc. (TSX-V:PINK)(OTC:PYNKF) (FSE:4PC) ("Perimeter" or the "Company"), a medical technology company driven to transform cancer surgery with ultra-high-resolution, real-time, advanced imaging tools to address high unmet medical needs, reported that it has entered into a subscription agreement pursuant to which an affiliate of Social Capital Holdings Inc. ("Social Capital") will make a strategic C$43.4 million investment in the Company (Press release, Perimeter Medical Imaging AI, DEC 15, 2021, View Source [SID1234597242]).

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Jeremy Sobotta, Perimeter’s Chief Executive Officer stated, "We believe Social Capital’s investment marks a transformative, pivotal event for Perimeter that will help accelerate our growth. This strategic partnering comes at a time when we are ramping up our Perimeter S-Series market development activities and commercialization efforts across the U.S., while also supporting the ongoing clinical development of our next-gen AI technologies. This financing provides us with the backing to execute upon our long-term vision to transform cancer surgery."

Chamath Palihapitiya, CEO of Social Capital, said, "Perimeter’s advanced imaging technology has the opportunity to materially improve cancer surgery outcomes. Today’s methods rely on contemporary imaging techniques, which often result in the need for additional surgery, increasing payer costs and potentially delaying subsequent treatment plans. This investment will support the commercial launch of Perimeter’s initial imaging device for breast cancer, but equally as important, we believe it can accelerate their path to become the standard of care for many other surgical applications in the future."

Social Capital has agreed to subscribe, on a non-brokered private placement basis (the "Private Placement"), for C$43.4 million in units of Perimeter at a price of C$3.00 per unit (each, a "Unit"), with each Unit consisting of one common share (each, a "Common Share") and a total of one warrant ("Warrant") to purchase an additional Common Share (a "Warrant Share"). 80% of the Warrants issued in the Private Placement will have a strike price of C$3.99 and 20% of the Warrants in the Private Placement will have a strike price of C$4.50. Half of the Warrants at each strike price will be subject to accelerated expiry if the 60-day volume weighted average trading price of Perimeter’s Common Shares is greater than the strike price during the applicable period. The other half of the Warrants will not be subject to accelerated expiry, and instead they may be exercised for cash or exercised using a cashless exercise feature at any time prior to expiry. Subject to the accelerated expiry clause described above, all Warrants will expire five years following the closing of the Private Placement.

Social Capital will also enter into an investor rights agreement with Perimeter at the closing of the Private Placement, which will provide Social Capital with the right to nominate one director to the board of Perimeter, with anti-dilution rights to participate in future financings, and with customary registration rights.

Perimeter may, but has not yet committed to, issue up to an additional C$7,000,000 million in Units on substantially the same economic terms as those issued to Social Capital.

The net proceeds of the Private Placement will be used for working capital, commercialization of Perimeter’s technology, clinical studies and the further development of Perimeter’s technology, and general corporate purposes.

About the Investment

Closing of the Private Placement is subject to the receipt of TSX Venture Exchange approval, the receipt of all necessary Perimeter shareholder approvals, and other customary closing conditions. The Private Placement will result in the creation of a new control person of Perimeter under Canadian securities laws as Social Capital will hold over 20% of the issued and outstanding shares of Perimeter, and accordingly, under TSX Venture Exchange policies, shareholder approval of the creation of the new control person will be required as a condition of closing, which will be sought by written consent. Roadmap Capital Inc., Perimeter’s largest shareholder, which owns or controls approximately 38% of the issued and outstanding Perimeter common shares, has signed a support agreement in favour of the Private Placement and has committed to sign a written consent resolution approving the Private Placement. Perimeter will provide further details on the shareholder approval in a subsequent news release. Social Capital is at arms length to Perimeter. The subscription agreement is also subject to a number of customary closing conditions, including the lack of any material adverse effect on Perimeter prior to Closing. The subscription agreement contains an outside date of January 31, 2021 for closing, which may be extended in limited circumstances. Social Capital’s board nomination and anti-dilution rights under the investor rights agreement will last so long as Social Capital holds at least 15% of the common shares of Perimeter on an undiluted basis, and Social Capital’s registration rights will last so long as Social Capital holds at least 10% of the common shares of Perimeter on an undiluted basis. A finder’s fee equal to 3% of the proceeds from the sale of Units to Social Capital is payable in respect of the Private Placement, which finders fee will be paid by issuing common shares of Perimeter ("Finder’s Shares") at $3.00 per share, subject to TSX-V approval.

The Common Shares comprising part of the Units, the Warrants and the Warrant Shares (if such Warrant Shares are issued before the date that is four months and one day following the applicable Closing Date) and the Finder’s Shares shall be subject to a hold period ending on the date that is four months and one day following the applicable Closing Date.

On December 15, 2021 BeyondSpring Pharmaceuticals (the "Company" or "BeyondSpring") (NASDAQ: BYSI), a global pharmaceutical company focused on the development of cancer therapeutics, reported new data highlighting the mechanism of action of plinabulin in the prevention of chemotherapy-induced neutropenia (CIN) at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, held virtually and in person in Atlanta, Georgia from December 11-14, 2021 (Press release, BeyondSpring Pharmaceuticals, DEC 15, 2021, View Source;utm_medium=rss&utm_campaign=beyondspring-pharmaceuticals-announces-new-clinical-data-confirming-plinabulins-fast-onset-mechanism-of-action-in-the-prevention-of-chemotherapy-induced-neutropenia-at-the-63rd-ash-annual-mee [SID1234597188]). The data demonstrate that adding plinabulin to a myelosuppressive regimen rapidly reversed (within 24 hours) neutropenia and leukopenia in the PROTECTIVE-1 and -2 clinical studies by protecting progenitor stem cells in the bone marrow.

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"This clinical data provides evidence confirming the hypothesized progenitor stem cell protective mechanism of action for plinabulin, which further validates the positive Phase 3 data from the PROTECTIVE-2 clinical program. These data also build upon the rapid effect seen in clinical trials to date and support the opportunity for enhanced CIN prevention care with plinabulin," said Dr. Douglas Blayney, professor of medicine at Stanford University Medical School and global principal investigator for the CIN studies. "These data provide a strong rationale for combining plinabulin with pegfilgrastim, since the latter has a mechanism of action exerting CIN prevention in week 2 of the chemotherapy cycle while plinabulin shows a week 1 benefit. This early CIN benefit is critically important because these white blood cells are the body’s main source of defense against infection. If a cancer patient gets an infection due to CIN, it may affect their ability to finish chemotherapy for cancer treatment."

Dr. Ramon Mohanlal, executive vice president of research and development and chief medical officer at BeyondSpring Pharmaceuticals, added, "This presentation at ASH (Free ASH Whitepaper) provides mechanistic support for the observed benefit of plinabulin in the prevention of CIN, a condition that still has unmet medical need, despite the availability of the standard of care CIN prevention drug, G-CSF. In addition, the rapid onset of action is critical since week 1 of each chemotherapy cycle is when more than 75% of CIN cases occur, even with G-CSF. Investigating the nuances of how and when plinabulin works is a continuous part of our work in understanding this multifaceted therapy. We look forward to sharing more of these insights with the oncology community in future studies."

This poster was presented on Sunday, December 12, 2021 and is available on the ASH (Free ASH Whitepaper) website.

Poster Title: Plinabulin Rapidly (within 24 Hours) Reverses Myelosuppression Induced by Chemotherapy
Abstract Number: 2056
Key Findings:

This new data analysis from the PROTECTIVE-1 and 2 studies aimed to further evaluate plinabulin’s fast onset mechanism of action (MoA) and potential progenitor stem cell involvement in plinabulin’s fast onset MoA.
The comparison was made between cancer patients receiving plinabulin 40 mg (n=228) or not receiving plinabulin (n=172), and with all patients receiving myelosuppressive chemotherapy (docetaxel with or without doxorubicin and cyclophosphamide). Plinabulin 40 mg was given 30 minutes after chemotherapy.
Plinabulin rapidly (within 24 hours) reversed chemo-induced myelosuppression in both the PROTECTIVE-1 and 2 human studies. Plinabulin-mediated increases in cell numbers are dose-dependent and correlated among cells of the myeloid, lymphoid and erythroid lineages.
Neutrophils (p<0.0001; increase by >3x10E9/L with plinabulin and decrease by >0.5x10E9/L without plinabulin)
Monocytes (p=0.0023)
Eosinophils (p=0.0775)
Basophils (p<0.0001)
The data suggest that plinabulin targets granulocyte-monocyte-progenitor (GMP) stem cells (N, M, B and E progenitor) as well as progenitor cells further upstream in the hematopoietic lineage.
About Plinabulin
Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent (SIMBA), which is a potent antigen presenting cell (APC) inducer. It is a novel, intravenous infused, patent-protected asset for CIN prevention and a Phase 3 anti-cancer candidate for non-small cell lung cancer (NSCLC) with recently released positive topline data. Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anticancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells, and the second is early-onset of action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs). Plinabulin received Breakthrough Therapy designation from both U.S. and China FDA for the CIN prevention indication. As a "pipeline in a drug," plinabulin is being broadly studied in combination with various immuno-oncology agents that could boost the effects of the PD-1/PD-L1 antibodies and re-sensitize PD-1/PD-L1 antibody-resistant patients.

On December 15, 2021 Endomag reported that A novel procedure could now spare breast cancer patients an invasive surgical procedure on their lymphatic system (Press release, Endomag, DEC 15, 2021, View Source [SID1234597246]). At MD Anderson Cancer Center, doctors have pioneered the Targeted Axillary Dissection (TAD) technique, where a tiny magnetic seed is placed into patient lymph nodes known to contain cancer. Following a course of neoadjuvant chemotherapy aimed to shrink or even eradicate their cancer, prior to surgery, this novel technique allows surgeons to monitor the response of targeted lymph nodes to the chemotherapy without the need for upfront invasive surgery, such as a complete axillary dissection.

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The magnetic seed, known as a Magseed allows surgeons to accurately remove the node marked prior to chemotherapy and remove it with minimal damage to healthy lymph node tissue.

Lymph nodes are a vital part of the system which helps the body to fight infection but are also the first structures breast cancer can spread to. In 40 to 75% of women, a course of chemotherapy before surgery can clear the nodes of cancer.1,2,3 However, until now, there has been no way to confirm the chemotherapy has been effective without removing a large number of lymph nodes from the underarm.

"The standard surgical approach for patients with breast cancer that has spread to the lymph nodes has been axillary lymphadenectomy (ALND), which involves removing most of the lymph nodes in the axilla," explains Dr Abigail Caudle, MD, who first pioneered the TAD technique at MD Anderson. "Unfortunately, this approach is associated with significant complications which can impact a patient’s quality of life including swelling, pain, and decreased range of motion. Some patients have an excellent response to chemotherapy and may have no disease remaining in the lymph nodes. We suspect that these patients may not benefit from having all of their lymph nodes removed, although the studies looking at this question are not yet available.

The challenge has been how to identify these patients that might benefit from less aggressive surgery. By specifically removing the exact lymph nodes that had confirmed cancer at the time of diagnosis, as well as the lymph nodes most likely to contain disease, we can now accurately assess whether there is cancer remaining in the lymph nodes and consider no further surgery if there is no evidence of cancer."

It is widely reported that up to 70% of women who have multiple nodes removed in an ALND procedure will develop complications linked to their treatment, such as the life-altering condition of lymphedema.4,5,6 Lymphedema is a condition where damage to the lymphatic system results in a build-up of lymphatic fluid in the body as a result of lymphadenectomy, causing lifelong symptoms of severe swelling, altered sensation, pain and limitations in range of motion.3. There are currently more than 10m people in the United States living with lymphedema,7 and for many patients, lymphedema is incurable.8

"There is a sea-change afoot in the treatment of breast cancer as patients become increasingly educated about the options available to prevent side effects of treatment. Foremost on this list are procedures and technologies that can prevent lymphedema—an incurable, debilitating, progressive and disfiguring swelling that can occur when the lymphatic system is damaged during surgery, radiation or chemotherapy. Women who win their battle against breast cancer routinely state that lymphedema can be worse than their cancer. Their cancer was cured. Their lymphedema is forever. In this modern world, every woman deserves the full benefits of our knowledge to mitigate onset of the life-long disease of lymphedema," explains William Repicci, LE&RN President & CEO

The Magseed marker, used by surgeons at MD Anderson, is the world’s most studied non-radioactive seed, with the technology available in over 40 countries around the world. Results from a series of past and ongoing multi-national studies 9,10 have demonstrated the ease and accuracy of marking positive lymph nodes with a Magseed marker with 100% success in surgical retrieval, negating the need for unnecessary node removal.

"This pioneering surgery exemplifies the importance of new technologies such as Magseed in moving breast cancer treatment forward." said Eric Mayes, CEO of Endomag. "These technologies have already helped over 200,000 patients globally access a better standard of cancer care. We’re committed to continually learning from physicians around the world and providing access to cutting-edge clinical applications that will make a difference to these patients for years to come.