On September 15, 2021 Aurinia Pharmaceuticals Inc. (NASDAQ: AUPH) (the "Company") reported that members of the senior management team will present at the following upcoming virtual investor conferences (Press release, Aurinia Pharmaceuticals, SEP 15, 2021, View Source [SID1234587732]):

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Oppenheimer Fall Healthcare Life Sciences & MedTech Summit Monday, September 20, 2021 at 2:55 pm ET. (access here)
Cantor Global Healthcare Conference on September 30, 2021 at 12:40 pm ET. (access here)
In order to participate in the audio webcasts, interested parties can also register and access presentations under "News/Events" through the "Investors" section of the Aurinia corporate website at www.auriniapharma.com. A replay of the webcasts will be available on Aurinia’s website.

On September 15, 2021 Amplia Therapeutics Limited (ASX: ATX), ("Amplia" or the "Company"), a company developing new drugs for the treatment of cancer and fibrosis, reported it has completed the design for a Phase 2 clinical trial of its Focal Adhesion Kinase (FAK) inhibitor, AMP945 (Press release, Amplia Therapeutics, SEP 15, 2021, View Source;[email protected] [SID1234587748]). This trial will be conducted in newly diagnosed patients receiving first-line therapy for pancreatic cancer.

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Amplia’s planned Phase 2 clinical trial will add AMP945 to chemotherapy with gemcitabine and nabpaclitaxel, which is a standard of care currently used to treat the majority of newly diagnosed advanced pancreatic cancer patients. In the trial, designated AMP945-202, AMP945 will be administered orally to patients prior to each dose of their standard gemcitabine/nab-paclitaxel chemotherapy. The design of this trial is based on studies conducted in collaboration with Professor Paul Timpson’s group at the Garvan Institute of Medical Research, Sydney, where it has been shown that intermittent dosing of AMP945 makes tumours more responsive to standard chemotherapy treatments in animal models of pancreatic cancer.

Conducting the Phase 2 clinical trial in first-line patients is expected to expedite recruitment for the trial and provides the best opportunity to detect any efficacy signal from the addition of AMP945 to chemotherapy. The ability to test AMP945 in a first-line setting is also made possible by the excellent safety and tolerability profile demonstrated in Amplia’s recent Phase 1 clinical trial.

Dr Adnan Nagrial, of Sydney’s Westmead Hospital and lead investigator on the trial, commented that "Patients with advanced pancreatic cancer have very limited treatment options and we desperately need new therapies with novel mechanisms of action. Based on the evidence we have seen so-far, FAK inhibitors deserve to be tested in the clinic and I am excited to be part of this trial".

The Phase 2 trial of AMP945 will be an open-label single arm trial conducted in two stages. In the first stage, an optimal dose of AMP945 will be selected and a preliminary assessment of efficacy will be performed in approximately 40 pancreatic cancer patients. In the second stage, up to an additional 24 pancreatic cancer patients will be recruited in order to increase confidence in the preliminary results. All patients are expected to receive multiple rounds of treatment.

The Company plans to initiate patient recruitment at Australian sites in the first quarter of 2022. Currently, the Company expects that recruitment will take 18-24 months but is working with vendors to accelerate key aspects of the trial. The primary endpoint for the trial will be based on the objective response rate from treatment compared to historical controls. In addition, multiple other signals of efficacy will be assessed in the trial’s secondary and exploratory endpoints including duration of response, disease progression rates, survival and effects on biomarkers of disease.

"Clinical evaluation of AMP945 as part of a first-line treatment for pancreatic cancer significantly de-risks the program and makes the drug relevant for a much larger patient base." said Dr John Lambert, CEO of Amplia Therapeutics. "If we are able to see positive signs that AMP945 improves the leading current treatment option we will commence discussions with regulators and potential partners concerning future trials required to support product approval."

This ASX announcement was approved and authorised for release by the Board of Amplia Therapeutics.

On September 15, 2021 PsiOxus Therapeutics, Ltd. (PsiOxus), a tumor re-engineering company, reported that they will present key safety and translational data from their first-in-human phase 1 FORTITUDE clinical study at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021 this week (Press release, PsiOxus Therapeutics, SEP 15, 2021, View Source [SID1234587766]). Data from the completed monotherapy dose-escalation part of the FORTITUDE study, initiated in 2019 to assess the safety and tolerability of the NG-350A T-SIGn vector, will be presented on Friday 16th September 2021, with the poster available in full at www.psioxus.com shortly afterwards.

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NG-350A is a T-SIGn vector designed to re-engineer cancers by selectively expressing a CD40 agonist monoclonal antibody, a potent activator of immuno-inflammatory responses, within the tumour microenvironment. PsiOxus is developing this agent as one of several products within its T-SIGn portfolio of vectors that combine systemic delivery with localized production of powerful transgene payloads to allow the selective re-engineering of both primary and metastatic tumors.

The data to be presented at the ESMO (Free ESMO Whitepaper) Congress show that IV delivery of NG-350A results in sustained elevations of inflammatory cytokines in the phase 1 FORTITUDE trial. In particular, marked and persistent dose-dependent increases in both IL-12 and IFNγ were observed after a single 1-week course of NG-350A, indicative of robust activation of antigen presenting cells via CD40 agonism generated within the tumor. Expansion of new T cell clones, a high proportion of which were new clones, was also observed following a single cycle of NG-350A. Safety data from the 25 patients treated with NG-350A as part of the now completed monotherapy dose-escalation part of FORTITUDE demonstrated that NG‑350A was well-tolerated, with few of the adverse events associated with systemic delivery of anti-CD40 agonists observed.

Together, these data suggest NG-350A contributes to the re-programming of the tumour microenvironment while avoiding the toxicity associated with systemic non-localized dosing of anti-CD40 antibodies.

"The headline data shared at the ESMO (Free ESMO Whitepaper) Congress confirms previous findings that our T-SIGn vector replicates selectively in primary tumor cells and metastases and persists for several months after intravenous delivery. Even more importantly, the biomarker data indicates that ongoing vector replication in tumors effectively translates into sustained production of the transgene payload, in this case a CD40 agonistic antibody. This translational data is a first in class demonstration of a downstream effect of tumor re-engineering, using T-SIGn vectors to turn the patient’s tumor cells into small drug factories," said Tom Lille, M.D., Ph.D., Chief Medical Officer, PsiOxus.

Based on these highly promising data, NG-350A will be assessed in combination with an anti–PD-1 checkpoint inhibitor in Part B of FORTITUDE.

On September 15, 2021 Researchers from the Case Comprehensive Cancer Center reported that uncovered the potentially important role of the protein-coding gene, MYO10, in tumor development and immune therapy response (Press release, Case Western Reserve University, SEP 15, 2021, View Source [SID1234587733]). Their findings were published today in Science Advances.

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The team, led by Youwei Zhang, an associate professor of pharmacology at the Case Western Reserve University School of Medicine, found breast tumors with high levels of MYO10—including the most malignant triple-negative breast cancers—responded favorably to immune checkpoint blockade (ICB) therapy, supporting the use of this therapy to treat these types of tumors.

ICB is an innovative treatment that uses medications known as immune checkpoint inhibitors—medications that can help the body’s immune system recognize and attack cancerous cells.

The team’s findings also suggest that the use of ICBs should be avoided in breast tumors with low MYO10 because these tumors actually grew larger after ICB therapy.

Studies found that high levels of MYO10 induce chronic inflammation in tumors, which reduces the ability of key immune cells—known as T cells—to slow tumor growth.

At the same time, however, this inflammatory environment in the tumor increased the ability of immune cells to provoke an immune response. This eventually allowed tumor cells to respond to ICB therapy, improving outcomes.

Proteins called interferon and interleukin—and other factors that regulate their production—are part of the body’s natural defenses. When they sense germs or cancer cells in the body, they boost the immune system, triggering killer immune cells to fight these invaders.

A model showing how the MYO10 protein regulates the inflammation and creates a favorable situation for immune checkpoint blockades.
A model showing how the MYO10 protein regulates the inflammation and creates a favorable situation for immune checkpoint blockades.
In this study, the researchers found that high levels of MYO10 increased the presence of interferons; conversely, low levels of MYO10 correlated with reduced production of interferons. These findings at least partly explain why MYO10-low tumors failed to respond to ICB therapy, the researchers explained.

Consistent with a chronic inflammation environment in tumors with high levels of MYO10 that led to loss of T cell function, treatment with aspirin to reduce inflammation significantly reduced the growth of breast tumors overexpressing MYO10.

This is consistent with studies showing that long-term use of aspirin or nonsteroidal anti-inflammatory drugs significantly reduced tumor risk for esophageal, colorectal and stomach cancers, as well as—to a smaller degree—in breast, lung and prostate cancers.

The team members further uncovered how MYO10 drives tumor growth. They found that MYO10 regulates the genome stability and cancer growth through mediating the nucleus shape. They also discovered that the protein level of MYO10 is critical for this function.

They went on to show how the protein recycling system tightly controls the expression level of MYO10. These findings support the tumor studies, highlighting the importance of MYO10 in tumor development and immune therapy response.

"This is the first study to link MYO10 with genomic instability and to validate the role of MYO10 in tumor development and immune therapy response," said Zhang, a member of the Molecular Oncology Program of the Case Comprehensive Cancer Center. "We will continue these studies and are eager to see how this knowledge can have a clinical impact on patient care. In addition, we hope that these findings will lead to more effective therapy options for breast cancer patients and the elimination of less effective treatments."

Study co-authors include: Mark Jackson, at the Case Comprehensive Cancer Center and Case Western Reserve School of Medicine; Franklin Mayca Pozo, Xinran Geng and Ilaria Tamagno from the Case Western Reserve School of Medicine; Ernest G. Heimsath and Richard Cheney from University of North Carolina Chapel Hill; and John Hammer, from National Heart, Lung and Blood Institute.

On September 15, 2021 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company") reported that it has completed enrollment of the pivotal Phase 3 SIERRA trial for Iomab-B, an Antibody Radiation Conjugate (ARC) comprised of apamistamab, a CD45 targeting antibody, and the radioisotope iodine-131 (Press release, Actinium Pharmaceuticals, SEP 15, 2021, View Source [SID1234587749]). The SIERRA trial is a 150-patient, randomized and controlled study conducted at 24 leading bone marrow transplant centers in the United States and Canada. SIERRA is the only randomized Phase 3 trial to offer bone marrow transplant (BMT) to patients with active, relapsed or refractory acute myeloid leukemia (AML) age 55 and above, which is the only curative treatment option for this patient population.

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(PRNewsfoto/Actinium Pharmaceuticals, Inc.)

Actinium expects to present data updates from the SIERRA trial in the fourth quarter of 2021 and to announce topline data for the primary endpoint of six-month durable Complete Remission (dCR) in mid-2022. These data are expected to support registration of a Biologics License Application (BLA) for Iomab-B.

Dr. Sergio Giralt, Deputy Division Head, Division of Hematologic Malignancies; Melvin Berlin Family Chair in Multiple Myeloma, said, "As an investigator in the SIERRA trial, I believe it is an important trial in the field of bone marrow transplant, as Iomab-B represents a potentially significant advancement for BMT conditioning. Having spent my career working to expand the use of transplant and improve patient outcomes, I know firsthand the value a targeted conditioning agent like Iomab-B can offer patients and transplant physicians. Given Iomab-B’s targeted nature, it has demonstrated the ability to produce effective myeloablation, even in patients with high disease burden, while also being well tolerated. This has shown to enable more patients, including those with significant comorbidities, to access bone marrow transplant and successfully engraft."

Dr. Avinash Desai, Actinium’s Executive Vice President, Clinical Development, Operations, stated, "We are thrilled that the SIERRA trial is now fully enrolled. Since joining Actinium last November, I have ensured our clinical, CMC and supply chain teams have been entirely focused on execution and on achieving this important milestone. Iomab-B was developed to address the significant unmet need of patients who could benefit and possibly be cured of their blood cancer with a bone marrow transplant but could not receive a transplant because non-targeted conditioning regimens could not produce a remission or are too toxic in this patient population. We are confident that Iomab-B will squarely addresses this unmet need given its targeted nature and ability to deliver high amounts of radiation directly to the bone marrow resulting in myeloablation while sparing healthy organs. The SIERRA trial was designed to evaluate the rate of dCR of at least six months in patients receiving Iomab-B and a BMT to those receiving salvage chemotherapy. With enrollment complete, we will turn our focus towards preparing a BLA submission with the goal of making Iomab-B available to the patients as soon as possible after receiving the topline results from the SIERRA trial. We sincerely thank the patients, their families, caregivers, staff and investigators that participated in this important study."

Sandesh Seth, Actinium’s Chairman and CEO, said, "Completion of SIERRA enrollment is a major milestone for Actinium. It has been exciting seeing the trial conclude with strong momentum under Dr. Desai’s leadership. Through strong interactions with our sites, our revitalized clinical team has been able to successfully surmount obstacles that arose from the third wave of the COVID-19 pandemic and recruit the last 25% of patients faster than any previous cohort of patients. Their performance is a testament that our execution has never been stronger. We are eager to present additional data from SIERRA later this year and look forward to reporting topline data next year. As we look ahead, our team will be actively preparing a BLA to support regulatory approval of Iomab-B in patients with active r/r AML and executing market access and pre-commercial activities to support a potential U.S. launch."

"In addition, we will explore opportunities to expand the use of Iomab-B in other indications to support our targeted conditioning strategic business unit vision. Given that Iomab-B is the only CD45 targeting agent in clinical development, and that CD45 is expressed in all blood cancers, we believe there is a significant market opportunity. This multi-indication opportunity excites us as our commercial efforts would target a concentrated number of transplant centers and physicians that we believe will result in significant operating leverage. Beyond targeted conditioning, we will continue to leverage our targeted radiotherapy expertise, particularly in the field in the field of Actinium-225 based alpha therapies, to be at the forefront of innovation focused on bringing value to patients and investors," concluded Mr. Seth.

Iomab-B SIERRA Engraftment and Safety Data and Highlights Through 75% Enrollment

(presented at the 2021 Transplantation and Cellular Therapy Annual Meeting)

– 100% (49/49) BMT access and engraftment rate for patients receiving a therapeutic dose of Iomab-B compared to 18% (10/57) of patients receiving physician’s choice of salvage therapy on the control arm

– 79% (89/113) of all patients enrolled on SIERRA were able to proceed to BMT despite being a patient population not considered eligible for BMT with standard approaches due to cross over

– Iomab-B delivers high amounts of targeted radiation to the bone marrow with minimal impact on other organs resulting in lower rates and severity of adverse events

Phase 3 SIERRA – 75% Enrollment Results

Baseline Characteristics

Iomab-B Arm
(N=56)

Conventional Care (CC) Arm
(N=57)

Age (years)
Median (Range)

63 (55-77)

65 (55-77)

Cytogenetic and
Molecular Risk1, 2

Favorable: 4%
Intermediate: 35%

Adverse: 61%

Favorable: 5%

Intermediate: 32%

Adverse: 63%

% Transplanted
Intent-to-Treat Group

88% (49/56)

18% (10/57)

64% (30/47)

Results

Underwent Iomab-B
based Conditioning
and BMT (N=49)3

Achieved CR
and received
standard of care
BMT (N=10)

Randomized to Conventional
Care and Crossed Over to
Iomab-B with BMT (N=30)4

Crossover Rate

n/a

n/a

64% (30/47)

% Transplanted

100% (49/49)

18% (10/57)

100% (30/30)

% Marrow Blast @ Randomization
Median (Range)

29% (4-95)5

20% (5-97)

28% (6-87)

Days to ANC Engraftment

14 (9-22)6

17 (13-83)7

14 (10-37)8

Days to Platelet Engraftment

18 (4-39)6

22 (8-35)7

19 (1-38)8

Days to BMT (Post Randomization)

30 (23-60)

67 (52-104)

62 (36-100)9

Myeloablative Dose Delivered to Bone
Marrow

14.7 (4.6-32) Gv

n/a

15.5 (6.3-42) Gv

592 (313-1013) mCi

646 (354-1027) mCi

100-day Non-Relapse Transplant-
Related Mortality

4%

(2/45 Evaluable)

20%

(2/10 Evaluable)

10.7%

(3/28 Evaluable)

1) Iomab-B arm: data unavailable (4) and patient was excluded (1)

2) Per NCCN guidelines version 3. 2020

3) No therapy dose (7) due to: declining KPS (4), infusion reaction (1), unfavorable biodistribution (1), post-randomization eligibility (1).
Two (2) did not receive DI and five (5) received DI without proceeding to TI.

4) Thirteen (13) patients ineligible for crossover due to: hospice care/progression (4), declined/ineligible for BMT (5), died pre-crossover
(4). Additionally, four (4) patients were eligible for crossover and did not receive Iomab-B due to declining KPS.

5) One (1) patient with 4% blasts in the marrow had circulating AML blasts

6) ANC engraftment data not available (4), platelet engraftment data not available (7)

7) ANC and platelet engraftment data not available (1)

8) ANC engraftment data not available (1), platelet engraftment data not available (2)

9) One (1) patient at 161 days had delayed transplant due to infection & respiratory failure, received Iomab & transplant when stable, not
included in range

Adverse Event

Underwent Iomab-B
based Conditioning and
BMT (N=49)1
% (N)

Achieved CR and received
standard of care BMT (N=10)
% (N)

Randomized to Conventional
Care and Crossed Over to
Iomab-B with BMT (N=30)2
% (N)

Sepsis

4 (2)

30 (3)

23 (7)

Febrile Neutropenia Gr
3-4

42 (20)

50 (5)

40 (12)

Mucositis Gr 3-4

10 (5)

30 (3)

17 (5)

Day +100 Non-Relapse
Mortality3

2/45
(4.4)

2/10
(20.0)

3/28
(10.7)

1) Adverse Event data available for 46 of 47 evaluable patients

2) Adverse Event data available for 27 of 30 evaluable patients

3) Iomab-B arm: 4 patients unevaluable. Conventional Care Arm: 4 patients unevaluable

Patient Group

No. of Patients

Radiation dose delivered to
the Marrow. Median

Radiation dose to GI tract.
Median

Iomab-B

49

14.6 Gy

2.8 Gy

About the SIERRA Phase 3 Trial

The SIERRA trial is a 150-patient, randomized clinical trial, studying Iomab-B compared to physician’s choice of salvage therapy in patients with active, relapsed or refractory acute myeloid leukemia (r/r AML) age 55 and above. In SIERRA, patients receiving Iomab-B, those achieving a remission after salvage therapy or those patients not achieving remission after salvage therapy that crossed over to receive Iomab-B were offered a bone marrow transplant (BMT), which is the only treatment option with curative potential for patients with active r/r AML. The SIERRA trial is the only randomized Phase 3 trial to offer BMT to this patient population. The control arm of SIERRA included over 20 single agents or combination treatment options based on physician’s choice which include salvage chemotherapy and recently approved targeted agents including Bcl-2 inhibitor (Venetoclax), FLT3 inhibitors and IDH 1/2 inhibitors as there is no standard of care for this patient population. The SIERRA trial was conducted at 24 sites in the United States and Canada.

About Iomab-B

Iomab-B (I-131 apamistamab) via the monoclonal antibody apamistamab, targets CD45, an antigen widely expressed on leukemia and lymphoma cancer cells, immune cells and bone marrow stem cells. Apamistamab is linked to the radioisotope iodine-131 (I-131) and once attached to its target cells emits energy that travels about 100 cell lengths, destroying a patient’s cancer cells and ablating their bone marrow. By carrying iodine-131 directly to the bone marrow in a targeted manner, Actinium believes Iomab-B may avoid the side effects of radiation on most healthy tissues while effectively killing the patient’s cancer (induction) and marrow cells (myeloablation) including those in bone marrow niches due to the "crossfire" effect enabled by the I-131 radioisotope.

Iomab-B was licensed from the Fred Hutchinson Cancer Research Center where it was studied in nearly 300 patients, in multiple clinical trials in 6 blood cancer indications. Iomab-B is being studied in the pivotal Phase 3 SIERRA (Study of Iomab-B in Relapsed or Refractory AML) trial, a 150-patient, randomized controlled clinical trial in patients with relapsed or refractory Acute Myeloid Leukemia (AML) who are age 55 and above. The SIERRA trial was conducted at 24 preeminent transplant centers in the U.S. and Canada. The primary endpoint of durable Complete Remission (dCR) at six months and a secondary endpoint of overall survival. Upon approval, Iomab-B is intended to prepare and condition patients for a bone marrow transplant, also referred to as a hematopoietic stem cell transplant, in a potentially safer and more efficacious manner than the non-targeted intensive chemotherapy conditioning that is the current standard of care in bone marrow transplant conditioning. A bone marrow transplant is often considered the only potential cure for patients with certain blood-borne cancers and blood disorders. Additional information on Iomab-B and the Phase 3 SIERRA clinical trial can be found at www.sierratrial.com.