California Prop 14 may change lives of sick kids, keep taxpayer funding of stem cell therapy research

Three-year-old Ava was constantly sick. Her gums were inflamed, and every time she got a scraped knee, it turned into a dangerous infection.

Her parents, Alicia and Jon Langenhop, were months pregnant with their third child when they learned that Ava’s constellation of symptoms added up to an extremely rare, inherited disorder of the white blood cells, called leukocyte adhesion deficiency-1. Although antibiotics and antivirals could prolong her life, the disease was considered fatal, usually before kindergarten.

Ava’s primary hope, doctors told the Langenhops, was a bone marrow transplant from someone who was a good match, probably a brother or a sister.

Two-year-old Olivia had inherited the same disease as her big sister. She had been hospitalized with infections, too.

The baby in Alicia’s belly would be the girls’ best hope. Since both parents were carriers of the rare genetic mutation, the new baby, a boy, had a 25% chance of inheriting it, too.

Alicia was still in the hospital last October when they found out baby Landon had the mutation. Around the same time, the couple learned of a research trial in California.

Children Ava, Olivia and Landon Langenhop were diagnosed with an extremely rare, inherited disorder of the white blood cells, called leukocyte adhesion deficiency-1. California Proposition 14, a citizen-initiated ballot measure, authorizes bonds continuing stem cell research.
Children Ava, Olivia and Landon Langenhop were diagnosed with an extremely rare, inherited disorder of the white blood cells, called leukocyte adhesion deficiency-1. California Proposition 14, a citizen-initiated ballot measure, authorizes bonds continuing stem cell research.

Doctors would take each child’s blood cells, fix the mutation and return them. It should be a permanent fix, with less risk than a bone marrow transplant because the healthy cells would be their own, so their bodies wouldn’t reject them as foreign.  

The approach had been tried in only one child, though.

This is the type of research reaching patients nearly two decades after President George W. Bush banned federal funding of stem cell research and 16 years after California residents approved a tax increase on themselves to support research.

Proposition 14 on Tuesday’s ballot asks whether Californians want to continue this work, providing $5.5 billion for stem cell research over the next three decades.

In the early 2000s, stem cell research was controversial because it often required the destruction of human embryos. Though embryonic stem cells remain essential for some therapies, in cases such as the Langenhops’, treatment focuses on manipulating a person’s own cells.

Stem cell science has made tremendous progress, but as in most new fields, the pace remains painstakingly slow. Every treatment has to be the subject of years of trial-and-error research, and many scientific hurdles linger. 

Stem cells have been used to treat rare diseases, such as severe combined immunodeficiency, also known as “bubble boy disease,” and they are being tested in more common conditions such as Parkinson’s disease, macular degeneration, Type 1 diabetes and even heart disease.

“Even if a subset of stuff in the pipeline goes all the way, it will change the world for patients who currently don’t have other good options,” said Sean Morrison, a stem cell biologist in Dallas.

“It’s a pivotal time in the field,” said

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Everything you need to know about the $5.5-billion stem cell measure

Scientists are learning more about how to harness stem cells to reverse heart failure, but treatments won't be widely available right away. Above, a stem cell researcher.
Scientists are learning more about how to harness stem cells to reverse heart failure, but treatments won’t be widely available right away. (Dennis Drenner / For The Times)

Proposition 14 would authorize the sale of $5.5 billion in general obligation bonds for the California Institute for Regenerative Medicine, known as CIRM, for stem cell studies and trials.

Here is a rundown of the ballot measure:

The measure

In 2004, voters approved a bond measure to pay for stem cell research.

Now, with the money from that bond running out, supporters of the state’s stem cell agency are asking taxpayers for a new infusion of cash.

With interest, the bond could cost the state $260 million per year, or $7.8 billion over the next 30 years, according to the nonpartisan Legislative Analyst’s Office.

Pro arguments

Proponents of Proposition 14 say the measure will help find new treatments and cures for chronic diseases and conditions, including cancers, spinal cord injuries, Alzheimer’s, Parkinson’s and heart disease. They say the previous bond advanced research and treatments for more than 75 diseases, including two cancer treatments for fatal blood disorders that were approved by the U.S. Food and Drug Administration.

Without new funding to keep the program going, supporters of Proposition 14 say, groundbreaking medical discoveries and lifesaving research will be slowed or stopped.

Anti arguments

Opponents say that the state shouldn’t take on new debt while facing a pandemic-induced deficit and that medical advances attributed to the previous stem cell bond have been overstated. In addition, opponents say CIRM has been hampered by conflicts of interest and too little oversight, neither of which are remedied by the ballot measure.

The campaign to pass the 2004 ballot measure told voters that the bond would save millions of lives and cut healthcare costs by billions. Critics say that’s not been the case to date, although supporters of this year’s measure note that they never intended those results within 16 years. While there is not much organized opposition, some newspaper editorial boards, including those at the Los Angeles Times and San Francisco Chronicle, have opposed it.

Reading list

With Prop. 14, California voters will be asked for more borrowing to keep stem cell research going

Explaining Prop. 14

Times columnist George Skelton assesses Prop. 14

The California stem cell program’s $5.5-billion funding request might be its downfall

California’s stem cell program faces an existential moment — and a chance for reform

When it comes to disease, stem cells are a game-changer, scientists say. This is why

This story originally appeared in Los Angeles Times.

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Genprex Unveils New Branding for Upcoming Combination Clinical Trials in Non-Small Cell Lung Cancer

New branding will support upcoming combination clinical trials, including the Company’s trial combining REQORSA™ immunogene therapy drug with AstraZeneca’s Tagrisso®, which received FDA Fast Track Designation earlier in 2020

Genprex, Inc. (“Genprex” or the “Company”) (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, today announced the launch of new branding for its upcoming oncology clinical trials combining its lead drug candidate, REQORSA(quaratusugene ozeplasmid), with AstraZeneca’s Tagrisso® (osimertinib), which received U.S. Food and Drug Administration (FDA) Fast Track Designation earlier this year, and for the combination of REQORSA with Merck’s Keytruda® (pembrolizumab), for the treatment of non-small cell lung cancer (NSCLC).

These trials will use the trial brand “Acclaim,” which the Company believes evokes its enthusiasm and the hope these trials represent for NSCLC patients and the oncology community. Acclaim-1 will be used to identify the REQORSA and Tagrisso combination clinical trial, and Acclaim-2 will be used to identify the REQORSA and Keytruda combination clinical trial.

“We are enthusiastically preparing for our upcoming clinical trials and are excited to launch the adoption of this branding,” said Rodney Varner, President and Chief Executive Officer of Genprex. “We believe the Acclaim brand communicates our passion for providing hope to NSCLC patients for important new treatment options in the fight against this devastating disease and aligns us with the clinical, medical and patient communities.”

The trial brand was developed in order to encourage early exposure of the Company’s clinical programs to the broad audience that Genprex’s business addresses, including patients, healthcare practitioners, clinical investigators, investors, employees and others. Genprex plans to initiate the Acclaim-1 clinical trial and the Acclaim 2 clinical trial in the first-half of 2021. Acclaim-1 is a Phase 1/2 clinical trial using a combination of REQORSA with Tagrisso in patients with late stage NSCLC with mutated epidermal growth factor receptors (“EGFRs”) whose disease progressed after treatment with Tagrisso. Acclaim-2 is a Phase 1/2 clinical trial using a combination of REQORSA with Keytruda in NSCLC patients who are low expressors (1 to 49%) of the protein, programmed death-ligand 1 (PD-L1).

About Genprex, Inc.

Genprex, Inc. is a clinical-stage gene therapy company focused on developing potentially life-changing therapies for patients with cancer and diabetes. Genprex’s technologies are designed to administer disease-fighting genes to provide new therapies for large patient populations with cancer and diabetes who currently have limited treatment options. Genprex works with world-class institutions and collaborators to develop drug candidates to further its pipeline of gene therapies in order to provide novel treatment approaches. The Company’s lead product candidate, REQORSA™ (quaratusugene ozeplasmid), is being evaluated as a treatment for non-small cell lung cancer (NSCLC). REQORSA has a multimodal mechanism of action that has been shown to interrupt cell signaling pathways that cause replication and proliferation of cancer cells; re-establish pathways for apoptosis, or programmed cell death, in cancer cells; and modulate the immune response against cancer cells. REQORSA has also

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Billions of Dollars for Stem Cell Research Institute On California’s November Ballot

SACRAMENTO, Calif.—In an election year dominated by a chaotic presidential race and splashy statewide ballot initiative campaigns, Californians are being asked to weigh in on the value of stem cell research—again.

Proposition 14 would authorize the state to borrow $5.5 billion to keep financing the California Institute for Regenerative Medicine (CIRM), currently the second-largest funder of stem cell research in the world. Factoring in interest payments, the measure could cost the state roughly $7.8 billion over about 30 years, according to an estimate from the nonpartisan state Legislative Analyst’s Office.

In 2004, voters approved Proposition 71, a $3 billion bond, to be repaid with interest over 30 years. The measure got the state agency up and running and was designed to seed research.

During that first campaign, voters were told research funded by the measure could lead to cures for cancer, Alzheimer’s and other devastating diseases, and that the state could reap millions in royalties from new treatments.

Yet most of those ambitions remain unfulfilled.

“I think the initial promises were a little optimistic,” said Kevin McCormack, CIRM’s senior director of public communications, about how quickly research would yield cures. “You can’t rush this kind of work.”

So advocates are back after 16 years for more research money, and to increase the size of the state agency.

Stem cells hold great potential for medicine because of their ability to develop into different types of cells in the body, and to repair and renew tissue.

When the first bond measure was adopted in 2004, the George W. Bush administration refused to fund stem cell research at the national level because of opposition to the use of one kind of stem cell: human embryonic stem cells. They derive from fertilized eggs, which has made them controversial among politicians who oppose abortion.

Federal funding resumed in 2009, and thus far this year the National Institutes of Health has spent about $321 million on human embryonic stem cell research.

But advocates for Proposition 14 say the ability to do that research is still tenuous. In September, Republican lawmakers sent a letter to President Donald Trump urging him to cut off those funds once again.

The funding from California’s original bond measure was used to create the new state institute and fund grants to conduct research at California hospitals and universities for diseases such as blood cancer and kidney failure. The money has paid for 90 clinical trials.

A 2019 report from the University of Southern California concluded the center has contributed about $10.7 billion to the California economy, which includes hiring, construction and attracting more research dollars to the state. CIRM funds more than 56,500 jobs, more than half of which are considered high-paying.

Despite the campaign promises, just two treatments developed with some help from CIRM have been approved by the Food and Drug Administration in the past 13 years, one for leukemia and one for scarring of the bone marrow.

But it’s a bit of a stretch for the institute to take

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Britain partners with Oxford firm to assess coronavirus vaccine T cell responses

LONDON (Reuters) – Britain on Thursday said it would partner with an Oxford-based firm to provide testing for the T cell response of coronavirus vaccine candidates to try to assess their immune responses.

T cell immunity is thought to be essential to protection against infection from the SARS-COV-2 coronavirus, and could provide longer term immunity than antibodies.

The UK Vaccine Taskforce has chosen Oxford Immunotec to supply T cell testing for its assessment of different vaccine candidates.

“It is important to be able to assess the different vaccines head-to-head and the T cell response is part of our portfolio of accredited assays that we are employing for cross comparisons,” Kate Bingham, chair of the UK Vaccines Taskforce, said in a statement.

Britain has signed supply deals for six different coronavirus vaccine candidates, including those being made by AstraZeneca <AZN.L> and Pfizer <PFE.N> and BioNTech <22UAy.F>, seen as among the frontrunners in the race for a vaccine.

Oxford Immunotec said its techonology platform enabled the centralisation of fresh blood samples from different locations to measure the T cell response in a standardised way.

It said the platform, known as T-SPOT, was being used to identify the T cells made in response to the pathogen that causes tuberculosis.

(Reporting by Alistair Smout; editing by Barbara Lewis)

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Affimed and NKMax America to Study the Combination of AFM24, an EGFR-Targeted Innate Cell Engager, with SNK01 Natural Killer Cell Therapy

  • Proof of Concept study to establish safety and recommended dose of Affimed’s innate cell engager (ICE®) AFM24 in combination with NKMax America’s Natural Killer (NK) cells in solid tumors

  • Pre-clinical data substantiates synergy between Affimed’s ICE® molecules and both NKMax America’s autologous and cryopreserved allogeneic NK cell therapy products

Heidelberg, Germany, and Santa Ana, California, October 20, 2020 – Affimed N.V. (NASDAQ: AFMD) and NKMax America Inc., both clinical stage biotech companies focused on harnessing the power of the body’s innate immune system, announced today that they entered into a clinical collaboration agreement to investigate the combination of AFM24, a CD16A/EGFR-targeted ICE®, with the autologous NK cell product SNK01. Pursuant to the collaboration, the companies plan to explore the combination in a first-in-human proof-of-concept (POC) trial in patients with EGFR-expressing tumors. The agreement follows a previous collaboration between the two companies in the preclinical setting to better understand the combined activity of their respective platforms. The results of the preclinical collaboration have shown substantive synergy between Affimed’s ICE® molecules and NKMax America’s autologous and cryopreserved allogeneic natural killer cell products.

Under the agreement, the companies will contribute their respective product candidates and resources towards submitting an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) and a subsequent clinical trial. The clinical trial will combine NKMax America’s SNK01 (enhanced natural killer cells) with AFM24 in the autologous setting with the option to expand the clinical trial to the allogeneic setting. The cost of the clinical study will be shared by Affimed and NKMax America. The agreement also provides for the opportunity to pursue further clinical study combinations with additional product candidates from both parties.

NKMax America has developed a proprietary NK cell expansion and activation technology platform which allows it to produce unprecedented commercial amounts of autologous and allogeneic NK cells from numerous donors that have near total expression of activating receptors like CD16A, NKG2D, NKp30 and NKp46. In addition, its unique technology increases the cytotoxicity of the expanded NK cells by nearly 8000 percent. In addition, the SNK01 product does not require lymphodepletion or cytokine support.

Using its ROCK® (Redirected Optimized Cell Killing) platform, Affimed has developed a novel pipeline of ICE® products. AFM24, a tetravalent, bispecific epidermal growth factor receptor (EGFR)- and CD16A-binding ICE®, is unique due to its activation of innate immunity to kill solid tumors, inducing both antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), whereas other EGFR-directed therapies rely heavily on signal transduction inhibition. A first-in-human Phase 1/2a open-label, non-randomized, multi-center, multiple ascending dose escalation/expansion study is underway evaluating AFM24 as monotherapy in patients with advanced solid EGFR-expressing malignancies whose disease has progressed after treatment with previous anticancer therapies.

“We believe combining ICE® molecules generated from our ROCK® platform with adoptive NK cell transfer can improve patient outcomes by ensuring patients have active and viable innate cells to be directed to the tumor and induce cytotoxic killing. In addition,

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Ultimovacs Announces Updated Positive Results from Phase I Trial Evaluating Universal Cancer Vaccine, UV1, in Non-Small Cell Lung Cancer

Ultimovacs ASA (“Ultimovacs”, ticker ULTIMO), today announced five-year overall survival data from the Phase I trial evaluating UV1 as maintenance therapy in patients with non-small cell lung cancer. The results confirm achievement of the primary endpoints of safety and tolerability and indicate encouraging initial signals of long-term survival benefit.

“Ultimovacs has established a growing body of clinical data demonstrating a strong safety and tolerability profile for UV1 and a range of preliminary efficacy signals in several cancer indications, all of which supports the further development of our proprietary cancer vaccine candidate,” stated Carlos de Sousa, Chief Executive Officer at Ultimovacs. “The long-term follow-up results announced today demonstrate that treatment with UV1 is safe both at the time of administration and throughout the follow-up period of at least 5 years. Non-small cell lung cancer highly expresses telomerase and remains an indication in great need of new treatment options for patients.”

In the study, a total of 18 non-small cell lung cancer patients whose disease had not progressed after receiving at least 2nd line treatment with chemotherapy were enrolled to receive UV1 monotherapy as maintenance treatment. Outcomes of the study included the safety and tolerability of UV1 as well as initial signs of clinical response. As per the cut-off date of June 2020, every patient in the trial reached at least 60-months of follow-up post treatment with UV1. At the five-years landmark, the Overall Survival (OS) rate was 33% and median Progression Free Survival (mPFS) was 10.7 months. Throughout the follow-up period, none of the patients experienced unexpected safety issues related to UV1. Further, none of the patients alive after 5 years have received other immunotherapy after the vaccination with UV1.

“At the time of the study initiation, there were no checkpoint inhibitors available for treatment of this patient population. For patients that received a second-line of chemotherapy the expected 5-year survival rate was less than 5 percent,” stated Jens Bjørheim, Chief Medical Officer at Ultimovacs. “While our Phase I study is non-randomized and conducted in a small population, it is promising to see that UV1 was safe and well-tolerated and that using UV1 as a maintenance therapy could potentially provide benefit to patients in need of novel approaches.”

Ultimovacs presented 48-months of follow-up data at the Society for Immunotherapy of Cancer’s (SITC) 34th Annual Meeting in November of last year.

About UV1

UV1 is a peptide-based vaccine inducing a specific T cell response against the universal cancer antigen telomerase. UV1 is being developed as a therapeutic cancer vaccine which may serve as a platform for use in combination with other immunotherapy which requires an ongoing T cell response for their mode of action. To date, UV1 has been tested in four phase I clinical trials in a total of 82 patients and maintained a positive safety and tolerability profile as well as encouraging signals of efficacy.

About UV1 Clinical Programs

As a universal cancer vaccine, UV1’s unique mechanism of action has the potential to

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EMA OKs First CAR T-Cell Therapy for Mantle Cell Lymphoma

The European Medicines Agency (EMA) today recommended granting conditional marketing authorization to brexucabtagene autoleucel (Tecartus), making it the first approved chimeric antigen receptor (CAR) T-cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) in the European Union.

Brexucabtagene autoleucel is the third CAR T-cell therapy to be recommended for approval in Europe, but the only one for this indication.

The agent was approved for the same use in the United States earlier this year and was described by one expert as representing a “new frontier” in the treatment of MCL.

The new agent addresses an unmet need in MCL for patients who relapse or progress despite available therapies.

The current standard of care for this cancer includes stem cell transplantation and various therapy regimens, including Bruton’s tyrosine kinase (BTK) inhibitors, all of which are often initially effective. However, patients commonly relapse or stop responding to treatment, according to the EMA.

“This opinion is an important milestone for patients in Europe living with relapsed or refractory mantle cell lymphoma,” said Ken Takeshita, MD, global head of clinical development at Kite, the agent’s manufacturer, in a press statement.

It is based on safety and efficacy results from the multicenter, single-arm ZUMA-2 trial in 74 adult patients with refractory or relapsed MCL who had received at least two prior therapies.

During the study’s 12-month follow-up period, 84% of patients had a partial response and 59% had a complete response.

The most common side effects are cytokine release syndrome, infections, and encephalopathy. Monitoring and mitigation strategies for these side effects are described in the product information and the agent’s risk management plan.

Further efficacy and safety data are being collected as part of long-term follow-up from the pivotal study and an additional registry-based study.

Brexucabtagene autoleucel was supported through EMA’s Priority Medicines (PRIME) initiative, which provides early and enhanced scientific and regulatory support to medicines that have the potential to address unmet needs.

Nick Mulcahy is an award-winning senior journalist for Medscape. He previously freelanced for HealthDay and MedPageToday, and had bylines in WashingtonPost.com, MSNBC, and Yahoo. Reach him by email and follow him on Twitter.

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