On April 19, 2023 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of targeted radiotherapies, reported the first ever data demonstrating the utility of Actimab-A to depleted myeloid derived suppressor cells (MDSCs), which are ubiquitously present within the solid tumor microenvironment as well as blood cancers (Press release, Actinium Pharmaceuticals, APR 19, 2023, View Source [SID1234630323]). The new data were showcased in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2023 Annual Meeting, which is being held April 14 – 19, 2023 in Orlando, Florida.

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Sandesh Seth, Actinium’s Chairman and CEO, said, "Significant research and development activities are being applied to understanding the complex biological activities within the tumor microenvironment in order to generate better treatment responses and patient outcomes. MDSCs are recruited to sites of chronic inflammation, such as the tumor microenvironment, where they exert immunosuppressive effects including inhibition of immune responses mediated by T cells, B cells, and NK cells. At Actinium, we believe Actimab-A can play an important role in the tumor microenvironment by depleting MDSCs, which express CD33, in a targeted manner. In doing so, Actimab-A can mitigate a major immunosuppressive contributor and potentially improve response rates as well as the duration of responses for a wide array of immunotherapies. With the substantial number of immunotherapies in development or currently in clinical use, we see multiple opportunities to synergize with immunotherapies such as checkpoint inhibitors and T and NK cell therapies. These data are an important step forward and we are excited to continue development of Actimab-A for MDSC depletion and beyond."

Highlights from the AACR (Free AACR Whitepaper) poster titled, "Targeting myeloid-derived suppressor cells with actinium-225 lintuzumab, a CD33 antibody radioconjugate to enhance antitumor immunity", include:

Actimab-A demonstrated efficient depletion of ex vivo human MDSCs derived from colorectal and lung cancer patient samples in vitro in addition to an in vivo humanized mouse model of Non-Small Cell Lung Cancer

Colorectal cancer blood MDSCs treated with Actimab-A were more effectively cleared (p<0.01) compared to depletion by Mylotarg, a CD33-targeted antibody-drug conjugate, highlighting the powerful cytotoxicity and potential therapeutic benefit of radiotherapy compared to naked antibodies or ADCs

Flow cytometry data confirmed an upregulation of CD33+ MDSCs in both lung and colorectal cancer patient samples compared to healthy donor controls. Following Actimab-A treatment in mice, a specific and robust depletion of ex vivo CD33+ MDSCs was observed

These results suggest that targeted blockade of MDSC activity via treatment with Actimab-A can alleviate their pro-tumorigenic and immunosuppressive activities to bolster the efficacy of immunotherapy such as checkpoint inhibitors.
The poster will be available on the presentations page of Actinium’s investor relations page of its website: View Source

On April 19, 2023 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of targeted radiotherapies, announces encouraging preclinical proof of concept data at a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2023 Annual Meeting being held April 14 – 19, 2023 in Orlando, Florida (Press release, Actinium Pharmaceuticals, APR 19, 2023, View Source [SID1234630322]). The poster showcased the robust anti-tumor effects of HER3-targeted radiotherapy using multiple therapeutic radionuclides in preclinical models of high unmet need malignancies.

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Highlights from the AACR (Free AACR Whitepaper) poster titled, "Novel HER3 targeting antibody radioconjugates, 225Ac-HER3 ARC and 177Lu-HER3 ARC, exhibit potent antitumor efficacy in HER3-positive solid tumors" include:

Actinium’s HER3-targeted radiotherapy displayed strong anticancer activity when conjugated to either alpha-emitting Actinium-225 or beta-emitting Lutetium-177 in models of two high unmet need cancers, highlighting its therapeutic potential for HER3+ malignancies

HER3-ARC showed strong target engagement and efficient cellular internalization with compelling cytotoxic activity against established in vitro cellular models

A single dose of HER3-ARC, conjugated to either Actinium-225 (p<0.0001) or Lutetium-177 (p<0.0001) showed highly significant reductions in tumor burden in a preclinical ovarian cancer model compared to bevacizumab, an anti-VEGF monoclonal antibody indicated in ovarian cancer

Promising antitumor activity displayed in a preclinical model of colorectal cancer, a highly aggressive malignancy, including a significant reduction in tumor volume (p<0.0001) when dosed with 225Ac-HER3-ARC

The consistent overexpression of HER3 in multiple solid tumor types including ovarian, renal, prostate, urothelial, breast, and lung cancers suggests broad utility of a HER3-targeted agent across oncology indications
"Actinium is committed to developing targeted radiotherapies for patients with unmet needs and our program targeting HER3, a validated, pan-cancer target, is a strong representation of our R&D capabilities", said Sandesh Seth, Actinium’s Chairman and CEO. "The new data from our HER3 program once again demonstrate the potent anti-tumor effect and broad utility of targeted radiotherapy in solid tumors. Building on our prior results in lung cancer models, we are excited by the highly significant reduction in tumor burden seen in ovarian cancer and colorectal cancer models, providing much improved treatment options to critical patients with poor clinical outcomes. These data also demonstrate our isotope-agnostic approach to targeted radiotherapy development enabling us to generate optimal therapies, given our strong, industry leading clinical experience with both beta and alpha therapies."

HER3 is a member of the EGFR family, a highly validated cancer target for which there are several approved therapies directed against EGFR and/or HER2. However, there are no approved therapeutics targeting HER3, which is upregulated in response to EGFR and HER2 therapies as part of acquired resistance and is associated with poor survival in multiple solid tumors including breast, colorectal, lung, ovarian and others.

The poster will be available on the presentations page of Actinium’s investor relations page of its website: View Source

On April 19, 2023 Onconova Therapeutics, Inc. (NASDAQ: ONTX), ("Onconova" or "the Company"), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported new preclinical data on narazaciclib in two poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Onconova, APR 19, 2023, View Source [SID1234630321]).

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"Data being presented at AACR (Free AACR Whitepaper) further highlight how narazaciclib’s differentiated inhibitory profile may allow it to overcome the shortcomings of FDA-approved CDK 4/6 inhibitors," said Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova. "Kinases recently identified as targets of narazaciclib, but not of the most widely prescribed CDK 4/6 inhibitor include BUB1, the overexpression of which was shown to be associated with poor survival in subtypes of endometrial and breast cancer. In addition, data featured in the AACR (Free AACR Whitepaper) posters provide additional evidence of narazaciclib’s potential to combine synergistically with therapeutic agents in a variety of drug classes. Looking forward, the learnings from these studies will be a valuable asset as we advance narazaciclib’s Phase 1/2a trial in endometrial cancer and evaluate potential opportunities for its clinical study in additional indications and with combination approaches to promote efficacy in resistant tumors."

Poster 5987: Differential targets engaged by narazaciclib in comparison to the approved CDK 4/6 inhibitors contribute to enhanced inhibition of tumor cell growth.

Featured in this poster are data characterizing narazaciclib’s mechanism of action and activity in preclinical cancer models. Results showed that, in addition to inhibiting kinases such as CDK 4/6, narazaciclib treatment led to the degradation of other kinases not targeted by the FDA-approved CDK 4/6 inhibitor palbociclib. These kinases included BUB1, the overexpression of which was shown to be associated with poor prognosis in breast cancer and uterine corpus endometrial carcinomas. Data from PYMT murine breast cancer cells showed a stronger induction in apoptosis (programmed cell death) with narazaciclib compared to palbociclib and another FDA-approved CDK 4/6 inhibitor, abemaciclib. In addition, data from multiple cell lines suggest that inhibiting autophagy may sensitize breast cancer cells to narazaciclib treatment.

Poster 5974: Synergistic activity of the CDK 4/6 antagonist narazaciclib (ON123300) with irreversible BTK inhibition in ibrutinib-resistant mantle cell lymphoma.

Data featured in this poster demonstrate narazaciclib’s potent antitumor activity against mantle cell lymphoma (MCL) cell lines, independent of their sensitivity to the FDA-approved Bruton’s tyrosine kinase inhibitor ibrutinib. Narazaciclib’s activity against MCL cell lines was shown to be superior to that of the FDA-approved CDK 4/6 inhibitors palbociclib and ribociclib, and similar to that of the FDA-approved CDK 4/6 inhibitor abemaciclib. Combining narazaciclib with ibrutinib led to synergistic increases in antitumor activity against both ibrutinib-sensitive and ibrutinib-resistant MCL cell lines. In addition, narazaciclib exhibited significant antitumor activity without detectable toxicity when combined with ibrutinib in an in vivo model of MCL (embryo chorioallantoic membrane xenograft model).

Copies of the AACR (Free AACR Whitepaper) posters will be available on the on the "Scientific Presentations" section of the Onconova website following the conclusion of the conference.

On April 19, 2023 Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, reported that the company is scheduled to release its first quarter 2023 financial results after the market closes on Wednesday, April 26, 2023 (Press release, Sangamo Therapeutics, APR 19, 2023, View Source [SID1234630320]).

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The Company will hold a conference call at 8:30 a.m. ET on Thursday, April 27, which will be open to the public. During the conference call, the company will review its financial results and provide business updates.

Participants should register for, and access, the call using this link. While not required, it is recommended to join 10 minutes prior to the event start. Once registered, participants will be given the option to either dial into the call with the number and unique passcode provided, or to use the dial-out option to connect their phone instantly. The link to access the live webcast can also be found on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations.

A replay will be available following the conference call, accessible under Events and Presentations.

On April 19, 2023 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs reported a poster presentation highlighting the results for ivospemin (SBP-101) as a polyamine metabolism modulator in ovarian cancer at the American Association for Cancer Research (AACR) (Free AACR Whitepaper), taking place April 14-19, 2023 (Press release, Panbela Therapeutics, APR 19, 2023, View Source [SID1234630311]). The work reflects the Company’s ongoing collaboration with Johns Hopkins University School of Medicine.

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"The treatment of C57Bl/6 mice injected with VDID8+ ovarian cancer with SBP-101 in combination with chemotherapy was observed to significantly prolong survival and decrease overall tumor burden," said Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela. "The continued work by collaborators at Johns Hopkins University School of Medicine is providing key data to support our efforts to initiate an ovarian cancer program this year."

"The results suggest that SBP-101 in combination with doxorubicin may have a role in the clinical management of ovarian cancer, in particular the platinum-resistant population where few options exist," said Dr. Simpson. "These studies are the basis for moving into a clinical trial program in ovarian cancer with a goal of developing effective novel therapeutics in combination with standard of care for patients with unmet medical needs."

The poster highlights the efficacy of SBP-101 in combination with standard of care chemotherapy agents used to treat platinum-resistant ovarian cancer. Treatment with gemcitabine, topotecan, and doxorubicin have been shown to significantly increase the in vitro toxicity of SBP-101 in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines. Paclitaxel and docetaxel have been shown to not have any added benefit in vitro to SBP-101 alone.

Utilizing the VDID8+ murine ovarian cancer model (ID8+ C57Bl/6 ovarian cells overexpressing both VEGF and Defensin), the efficacy of SBP-101 in combination with either gemcitabine, topotecan, or doxorubicin was evaluated. Gemcitabine and topotecan alone had little effect on the overall survival of the mice, whereas either SBP-101 or doxorubicin treatment alone significantly increased median mouse survival time. The addition of SBP-101 improved the survival of mice treated with any of the three chemotherapeutics. The SBP-101 and doxorubicin combination mice had the greatest survival time with a 265% increase in median survival compared to untreated animals.

Additionally, combining DFMO with ivospemin in vitro resulted in a cooperative antiproliferative response. DFMO has been shown to be well tolerated and can influence immune cells to promote a more immune-friendly tumor microenvironment. Future experiments will evaluate the effect of adding DFMO to ivospemin treatment as well as the influence on immune cells within the tumor microenvironment.

The poster concludes that the treatment of C57Bl/6 mice containing VDID8+ ovarian cancer with SBP-101 in combination with doxorubicin significantly prolonged survival and decreased overall tumor burden. Future studies will be designed to evaluate the effects of SBP-101 in combination with other polyamine metabolism modulators as well as with immune modulators. Details of the presentation are as follows:

Poster Presentation

Title: Evaluating the efficacy of spermine analogue ivospemin (SBP-101) in combination with chemotherapy in ovarian cancer
Session Category: Experimental and Molecular Therapeutics Session
Title: Novel Antitumor Agents, PI3K/AKT Inhibitors, Proteasome Inhibitors, and Topoisomerases Abstract #: 4944