Inovio Presents Cancer Killing Data of DNA-Encoded Bi-specific T Cell Engagers

Data demonstrates tumor-clearing ability of Inovio’s dBiTE technology in preclinical cancer model

Inovio Pharmaceuticals, Inc. (INO) announced today the company’s novel DNA-Encoded Bi-specific T Cell Engagers (dBiTEs^™) generated potent anti-tumor activities in a preclinical study. Results were presented as a poster at the American Association for Cancer Research (AACR) Annual Meeting in Atlanta. For this study, Inovio, with its collaborators at The Wistar Institute, developed a novel dBiTE targeting the HER2 molecule which was tested in therapeutic models for the treatment of ovarian and breast cancers. Importantly, just a single dose of Inovio’s HER2 dBiTE resulted in high levels of corresponding BiTE in mice for four months, far exceeding what is typically displayed with conventional BiTE’s short half-life of only a few hours. The HER2 dBiTE effectively generated T cell cytotoxicity against HER2-expressing tumor cells resulting in a near-complete tumor clearance.  Also presented was Inovio’s CD19 dBiTE which can kill B cell cancers by targeting B cell specific marker CD19.

Dr. J. Joseph Kim, Inovio’s President and CEO, said, “In layman’s terms, dBiTEs are like a double-sided tape that binds to a tumor and to a cancer-killing T cell.  By allowing the products be expressed directly and efficiently in the patient, our dBiTEs could finally fulfill the therapeutic promise of BiTEs. Based on these promising preclinical results, we are rapidly preparing for the clinical development of our dBiTE candidates, as well as constructing more cancer tumor targeting dBiTE candidates using our transformative dBiTE platform.”

Dr. Kim added, “Leveraging Inovio’s in vivo synthetic nucleic expression platform, we have shown that just one dose of Inovio’s dBiTE could generate corresponding BiTEs at high levels in mice for several months, demonstrating a dramatic advantage over conventional BiTEs.  Our CD19 dBiTE has the potential to treat multiple B cell cancers and to compete favorably with CD19 CAR-T products with potentially improved tolerability and safety profiles. Similarly, the HER2 dBiTE could be used to treat multiple solid tumors which express HER2 such as breast, ovarian, and gastric cancers.”

BiTEs are a class of artificial bi-specific monoclonal antibodies that has the potential to transform the immunotherapy landscape for cancer. They direct a host’s immune system, more specifically the T cells’ cytotoxic activity, against cancer cells. BiTEs have two binding domains. One domain binds to the targeted tumor (like HER2 or CD19 expressing cells) while the other engages the immune system by binding directly to CD3 molecules on T cells. This double-binding activity drives T cell activation directly at the tumor resulting in a killing function and tumor destruction.

The biggest drawback of conventional protein-based BiTEs is the delivery and expression. The BiTEs have a half-life of only about two hours, which requires patients to undergo continuous intravenous infusion for several weeks to maintain therapeutic levels, making treatment adherence more difficult and resulting in high levels of infusion-associated adverse events. In addition, just like other traditional monoclonal antibodies, conventional BiTEs are also manufactured in bioreactors, typically requiring costly large-scale manufacturing facility development and laborious production as well as having to deal with improper product folding and stability. They must also be kept and distributed frozen at all times. These difficulties collectively have limited the development and commercialization of conventional BiTEs as only one licensed product is currently on the market (BLINCYTO^® (blinatumomab)).

Inovio’s dBiTE is a new transformative application of Inovio’s dMAb™ platform. The dBiTEs share many advantages of Inovio’s dMAbs as they both are composed of engineered DNA sequences which encode two antibody fragments. When administered by Inovio’s CELLECTRA^® delivery device, the patient’s own cells become the factory to manufacture functional BiTES encoded by the delivered dBiTE sequences.

Inovio’s dBiTEs provide major potential advantages over a conventional protein-based BiTE therapy because of dBiTEs’ better product expression and availability as well as simplicity in administration and manufacturing.  Inovio has demonstrated that a single dose of dBiTE construct delivered with CELLECTRA^® expressed the product at high levels in mice for four months. Inovio’s dBiTEs are developed with simplified design using novel plasmid vectors and unique formulations allowing for rapidity of development, long-term product stability at refrigeration, ease of validated and scalable manufacturing and deployability.

https://finance.yahoo.com/news/inovio-presents-cancer-killing-data-114500102.html

How Much Does Medicare Spend on Insulin?

The rising cost of prescription drugs is currently a major focus for policymakers. One medication that has come under increasing scrutiny over its price increases is insulin, used by people with both Type 1 and Type 2 diabetes to control blood glucose levels. Among people with Medicare, one third (33%) had diabetes in 2016, up from 18% in 2000. The rate of diabetes is higher among certain groups, including more than 40% of black and Hispanic beneficiaries. Although not all people with diabetes take insulin, for many it is a life-saving medication and essential to maintaining good health. Three companies—Eli Lilly, Novo Nordisk, and Sanofi—manufacture most insulin products, and there are no generic insulin products currently available, despite the fact that insulin was discovered in the 1920s. Committees in both the House and the Senaterecently convened hearings on prescription drug costs that focused on rising insulin prices and affordability concerns for patients, and congressional investigations are underway.

This data note examines spending on insulin by Medicare and beneficiaries enrolled in private Part D drug plans, based on data from the Centers for Medicare & Medicaid Services (see Data and Methods). Because drug-specific rebate data for Medicare are proprietary, the analysis examines Medicare spending without rebates, but also uses average Part D rebates reported by Medicare’s actuaries to illustrate the potential effects on total Part D insulin spending. While rebates may help to lower Part D premiums, they do not lower enrollees’ out-of-pocket drug costs, which are based on list prices.

Key Findings

• Total Medicare Part D spending on insulin increased by 840% between 2007 and 2017, from $1.4 billion to $13.3 billion (Figure 1)—including what Medicare, plans, and beneficiaries paid.

• With rising prices and the introduction of more costly insulin products over time, average total Medicare Part D spending per user on insulin products increased by 358% between 2007 and 2016, from $862 to $3,949.
• Aggregate out-of-pocket spending by Part D enrollees on insulin quadrupled between 2007 and 2016, from $236 million to $968 million, reflecting both an increase in the number of users and price increases for insulin. Among enrollees without low-income subsidies, average per capita out-of-pocket spending on insulin nearly doubled between 2007 and 2016 (from $324 to $588; an increase of 81%).
• Among all insulin products, Lantus Solostar, a long-acting insulin manufactured by Sanofi, accounted for the largest share of both total Part D spending and out-of-pocket spending by enrollees who used insulin. Spending on Lantus Solostar, which was used by 1.1 million Part D enrollees in 2017, accounted for 20% of total Part D spending on insulin therapies in 2017 and 25% of out-of-pocket spending on insulin by non-low income subsidy enrollees in 2016.

Total Medicare Part D Spending on Insulin

According to our analysis, total Medicare Part D spending on insulin increased by 840% between 2007 and 2017, from $1.4 billion to $13.3 billion—including what Medicare, plans, and beneficiaries paid. In light of rising prices for existing insulin products and the introduction of more costly insulin therapies over time, average annual total Part D spending on insulin products per user increased by 358% between 2007 and 2016—from $862 to $3,949—while average total Medicare Part D spending per insulin prescription increased by 280% over these years—from $96 to $363 (Figure 2).

The total number of Part D enrollees using any insulin therapy nearly doubled between 2007 and 2016, from 1.6 million enrollees to 3.1 million—a much smaller increase in percentage terms (86%) than the percent increase in total Part D spending on insulin over the 2007-2016 period (753%) (Table 1). The total number of insulin prescriptions covered by Part D also increased over these years (from 14.8 million in 2007 to 33.3 million in 2016), but the percentage increase (125%) was also substantially lower than the percent increase in total insulin spending.

Total Part D spending on top insulin therapies. In 2017, the top five insulin therapies covered under Part D accounted for 62% of total Part D spending on insulin, or $8.2 billion out of the $13.3 billion total spending on insulin (Figure 3). Among all insulin products, Part D spending was highest for Lantus Solostar, a long-acting insulin manufactured by Sanofi, with $2.6 billion in Part D spending in 2017. This one drug alone, used by 1.1 million Part D enrollees in 2017, accounted for 20% of total Part D spending on insulin that year. Lantus Solostar was also among the top five drugs overall in terms of total Part D spending in 2017.

Average total Part D per capita costs for insulin therapy in 2017 ranged from $693 for Humulin R, a short-acting regular insulin manufactured by Eli Lilly—used by 102,000 Part D enrollees in 2017—to $10,014 for Humulin R U-500, a concentrated regular insulin for people who need large doses of insulin, also manufactured by Eli Lilly—used by 14,500 beneficiaries in 2017.

Total Part D spending by insulin manufacturer. In 2017, total Part D spending on all of the different insulin products from the three main manufacturers was $5.5 billion for Novo Nordisk, $4.8 billion for Sanofi, and $3.0 billion for Eli Lilly (Figure 4). Between 2007 and 2017, spending on insulin therapies from all three manufacturers increased dramatically. Over this time period, cumulative total Part D spending was $27.0 billion for insulin products from Novo Nordisk, another $27.0 billion for Sanofi, and $15.0 billion for Eli Lilly.

Trends in insulin spending per dosage unit. Of the 22 insulin therapies listed in the CMS Part D drug spending dashboard in both 2013 (the first year of dashboard data) and 2017 (the most recent year), 19 products had increases of more than 10% in annual Part D spending per dosage unit between 2013 and 2017, according to CMS estimates (Table 2). Six insulin products had increases of more than 10% in average spending per dosage unit between 2016 and 2017 alone (Figure 5).

These percentage increases in average spending per dosage unit for insulin products represent price increases that can translate to large increases in total spending per claim over time—even if the change in average spending per dosage unit measured in dollars may be relatively low—since there are typically multiple dosage units associated with each claim. For example, while Afrezza has the lowest average spending per dosage unit in 2017 of all the insulin products in the CMS dashboard data ($3.54), the 2016-2017 change of 21.6% was the largest in percent terms—and it translates into a large difference in spending per claim for Afrezza between 2016 and 2017—from $566 per claim in 2016 to $690 per claim in 2017, a $124 increase (Table 2).

Out-of-Pocket Spending on Insulin by Medicare Part D Enrollees

Part D enrollees’ total annual out-of-pocket costs for insulin. Since Medicare Part D plans cover a portion of enrollees’ total drug costs, enrollees pay less than the retail price of drugs covered by their plan, and those who receive Part D low-income subsidies (LIS) face relatively low out-of-pocket costs. Still, in the aggregate, out-of-pocket spending among all Part D enrollees on insulin quadrupled between 2007 and 2016, from $236 million to $968 million, reflecting both an increase in the number of users and price increases for insulin (Figure 6). Between 2007 and 2016, Part D enrollees spent a combined $5.5 billion out of pocket on insulin therapy.

Part D enrollees’ average per capita out-of-pocket costs for insulin. Among Part D enrollees who did not receive LIS, average per capita out-of-pocket spending for insulin alone was $588 in 2016, but including costs for all other prescriptions, total per capita out-of-pocket spending among those who used insulin was $1,334. Non-LIS enrollees’ average per capita out-of-pocket spending on insulin in 2016 was nearly double the amount in 2007 ($324; an increase of 81%).

For several insulin products, average per capita out-of-pocket spending by non-LIS enrollees increased by more than 100% between 2007 and 2016; for example, average per capita out-of-pocket spending on Lantus Solostar increased by 291% from $106 to $413 (Figure 7).

In 2016, average annual per capita out-of-pocket spending by non-LIS enrollees who used insulin therapies ranged from $110 for Levemir Flexpen, a long-acting insulin manufactured by Novo Nordisk, to $822 for Humulin R U-500 (Table 3).

Part D enrollees’ out-of-pocket spending on top insulin therapies. In 2016, the top five insulin therapies accounted for 67% of aggregate out-of-pocket spending on insulin by non-LIS enrollees that year, or $0.6 billion out of the $0.9 billion in out-of-pocket spending on insulin by non-LIS enrollees (Figure 8). Aggregate out-of-pocket spending was highest for Lantus Solostar, accounting for 25% ($230 million) of non-LIS enrollees’ total out-of-pocket spending on insulin therapy in 2016.

Illustrating the Potential Effect of Rebates on Total Insulin Spending

Our analysis is based on retail claims data and aggregated spending data that do not take into account manufacturer rebates and discounts to plans, which are considered proprietary and therefore not publicly available. There is data suggesting that insulin manufacturers have provided large rebates and discounts to payers that have produced net prices that are significantly lower than the high list prices that have attracted public scrutiny. Regardless of the magnitude of rebates for insulin products, however, rebates do not help to lower enrollees’ out-of-pocket costs for insulin. This is because the amount that enrollees pay out of pocket is either a flat dollar copayment (depending on their plan’s cost-sharing design) or, if they are paying full cost in the deductible phase or a coinsurance amount, their cost is based on pre-rebate list prices rather than post-rebate net prices.

Because CMS does not disclose drug-specific rebates, we are unable to know exactly the degree to which our estimates of total Part D spending on insulin therapy might overstate actual costs to Medicare and plans. We can approximate the potential effect of rebates on total Part D spending by assuming that all Part D plans had received for all insulin products the average rebate reported by Medicare’s actuaries each year between 2007 and 2017. Based on this assumption, insulin spending would have increased from $1.3 billion in 2007 (applying the 9.6% average rebate in 2007) to $10.3 billion in 2017 (applying the 22.8% estimated average rebate in 2017). This amounts to a 702% increase in total Part D spending on insulin between 2007 and 2017, compared to an 840% increase based on the pre-rebate total spending amounts ($1.4 billion and $13.3 billion, respectively). If actual rebates for insulin products were larger than these averages, total spending would be lower than these estimates.

Implications

Rising prices for insulin have attracted increasing scrutiny from policymakers in recent months. Our analysis demonstrates that rising insulin prices since 2007 have translated into significantly higher out-of-pocket spending for beneficiaries in Medicare Part D plans and higher spending for the program overall (not taking into account rebates). The number of people Medicare covers for insulin therapy has increased as the number of Medicare beneficiaries with diabetes has risen. Average annual total Part D spending per insulin user increased by 358% between 2007 and 2016, while average out-of-pocket costs for insulin by non-low income subsidy Part D enrollees nearly doubled.

Members of Congress and the Trump Administration have introduced several proposals that could help to address concerns about rising prices for insulin products and affordability concerns for patients, including banning rebates from drug manufacturers unless they are shared directly with patients at the point of sale, taking steps to increase the availability of generic products, allowing Medicare to negotiate drug prices, and allowing patients to import drugs from other countries. Rising prices for insulin therapy in recent years and the resulting increases in Medicare Part D and beneficiary out-of-pocket spending illustrate why the cost of prescription drugs is an ongoing concern for patients and public and private payers, and a pressing issue for policymakers.

https://www.kff.org/medicare/issue-brief/how-much-does-medicare-spend-on-insulin/

Nobel Prize winner argues banning CRISPR babies won’t work

Scientists are vigorously debating how, and if, they can put the human gene-editing genie back in the bottle.

There is widespread agreement that it’s currently “irresponsible” to make heritable changes in human cells. Gene editors, even the much lauded CRISPR/Cas9 molecular scissors, have not yet been proven safe and effective enough to use to alter genes in the human germline; embryos, eggs, sperm or the cells that give rise to eggs and sperm. But that didn’t stop Chinese scientist Jiankui He from announcing in  2018 the births of two gene-edited babies.

Now in the wake of almost universal outrage over He’s actions, efforts are under way to prevent others from doing the same thing.

Some scientists have recently proposed a temporary moratorium on editing that would result in babies that carry heritable changes. Such a ban would last for perhaps five years to buy enough time to improve the technology and to allow for public debate (SN Online: 3/13/19) .

An advisory committee to the World Health Organization has alternatively proposed a global registry of work on human gene editing. Such a database would provide transparency and a better understanding of the state of gene-editing science, committee representatives said in a news conference March 19.

Science News talked with Nobel laureate David Baltimore, who is president emeritus of Caltech, about the ongoing debate. Baltimore, a virologist and immunologist, chaired two international summits on human gene editing. The interview has been edited for brevity and clarity.

SN: You’ve come out in the past as not being in favor of a moratorium. Why?

Baltimore: It’s largely a semantic issue. Statements made after the first summit and the second summit have avoided using the term moratorium. Consciously. Because that word has been associated with very firm rules about what you can do and what you can’t do.

I fully agree — and the whole group of us involved in the summits agree — that we’re not ready to be doing germline modification of humans, if we ever are. You might say, “Well, that’s a moratorium,” and, in a sense, it is. I don’t have a big argument about that.

But the important point is to be flexible going forward. That’s what’s wrong with a moratorium. It’s that the idea gets fixed in people’s minds that we’re making firm statements about what we don’t want to do and for how long we don’t want to do it.

With a science that’s moving forward as rapidly as this science is, you want to be able to adapt to new discoveries.

— David Baltimore

With a science that’s moving forward as rapidly as this science is, you want to be able to adapt to new discoveries, new opportunities and new understandings. To make rules is probably not a good idea.

What’s a good idea is to be on top of a changing environment and to adjust to it as time goes by. And that’s both an ethical environment and a practical environment of the mechanics of gene editing.

SN: Would a global registry of all gene-editing experiments help?

Baltimore: A gene-editing event in which a human being’s genes have been modified, or in which a child’s genes have been modified, is something that will be passed on through the rest of time. It is now part of the heredity of the human species. If we don’t know it’s happened, we don’t know that [edited] gene is there, so we can’t identify the effect of having that [altered] gene.

So I think it is important that there be a registry of all gene-editing events, so that we can follow, over time, the consequences of those modified genes.… It is important [to] follow these children as they get older. You just want to make sure there is not some sort of untoward medical aspect to it, and second of all, to know what genes have been modified.

A registry would be very important for germline modifications. For somatic modifications [non-heritable edits in DNA of children’s and adults’ body cells], it’s not important, any more than for any other medical procedure, because it really isn’t any different from any other medical procedure.

SN: Are there similar registries for other types of research?

Baltimore: There is a global registry of clinical trials. I don’t know of another global registry that focuses on a particular therapeutic activity. On the other hand, there is nothing quite similar to gene editing that has ever been done before, so it would be reasonable to create it.

GOING ROGUE Despite widespread agreement that human gene editing isn’t safe, Jiankui He secretly altered genes in human embryos, which resulted in the birth of two babies last year. The incident has scientists debating how to stop other researchers from mimicking He’s actions.

IRIS TONG/VOA

SN: Can rogue activity, such as He’s creation of gene-edited babies, be prevented?

Baltimore: We want to create an environment where it’s very clear that we shouldn’t be moving ahead right now. [But] we can’t absolutely prevent that. You can’t prevent murder by having a law against murder. It still happens. Laws aren’t ways of preventing something; they are ways of indicating society’s opinion, and to take a person who has done it out of circulation if they’re a danger, but you don’t prevent the actual event from happening.

SN: What is the potential impact of individual governments or an international treaty restricting gene editing?

Baltimore: It could hold back the science. Right now there are many countries that have outlawed [germline editing] and the way they have phrased it prevents certain kinds of experimental work from being done. That is unfortunate, because I think we want to move forward with experimentation.

In the United States, you can’t do anything that modifies an embryo [paid for] with federal funds. But you can with private funds, so we are moving forward in the United States, using nonfederal money.

[In the moratorium proposal], they talk about individual countries making their own decisions, and I think that’s how it has to happen. It’s very hard to imagine a treaty with all of them and all the complications surrounding this issue. It would take so long, it would be out-of-date before it was passed.

I don’t see how we could prevent a country from saying it’s their position that germline editing should be allowed. There would be a lot of debate about that and such a country would find itself in the position of being an international outlier, and [might] not want to be that, so there would be a lot of pressure to conform. But we just don’t have the mechanism for international law beyond treaties.

SN: Do you envision a day when gene editing will be safe and effective enough to use for germline modifications?

Baltimore: I do.

SN: When?

Baltimore: You never know, because it depends on new technological innovations. They could happen tomorrow or they could not happen for years. It probably isn’t a matter of more than a few years.

SN: Has there been enough public education and debate that society will be ready for germline modification?

Baltimore: There are couples today who would like to have a child that inherits their genes, but among their genes, there is one [mutated gene] they would not like their offspring to inherit. If we could guarantee that the offspring would not inherit a mutated gene, they would then be able to have the child they want to have. They would be able to say to a physician, “Is there a procedure that could safely give us the child we want?”  I think when the answer to that question is “yes,” there will be tremendous pressure on the medical community to carry out gene modification.

At that point, we’ll have to balance the desires of couples to have children without mutated genes with the fact that this is a new kind of procedure that we don’t have a lot of experience with, and that some people may think is inappropriate. In general, people are responsive to the desires and needs of these couples. I think they will say this is something we should do.

ONE FOR ALL Doctors can test whether an embryo carries harmful genetic variants by removing one or more cells from an early embryo (shown) and testing the DNA of those cells. The process, called preimplantation genetic diagnosis, allows doctors to weed out embryos that carry genetic diseases.

JUAN GAERTNER/SCIENCE SOURCE

SN: Some people argue that it’s already possible to have a baby without a genetic disease through preimplantation genetic screening. So would germline gene editing be restricted to very specific cases?

Baltimore: It depends on what’s safest and most effective. If embryo selection can give us a very high percentage elimination of the gene, then we can do it by embryo selection. Today, the probability of getting a good implanted embryo that comes to term is about 25 percent. So 75 percent of couples that have a procedure don’t get an offspring, so it’s not very effective. Some people say, “Why don’t you just concentrate on making it more effective?” That would be a good thing, but we don’t know that you can. It really comes down to what works and what solves the problem.

SN: Are there any issues that need to be talked about more?

Baltimore: I think the biggest impediment to actually using the technology is the danger of mosaicism: embryos in which some cells are modified and some cells are not, and we don’t know which is which. We have not yet solved that problem.

There’s nothing like actually moving ahead [with research] to teach us what the actual pitfalls are.

— David Baltimore

There was a paper a year or more ago in Nature that claimed to have minimized mosaicism, but many people are doubtful that that paper is exactly right (SN Online: 8/8/18). So until we get that ambiguity solved, I don’t see how we can go forward. There are ways on the drawing boards to solve that problem, but they’re not in actual practice.

SN: Are there any other pitfalls we should be aware of?

Baltimore: There’s nothing like actually moving ahead [with research] to teach us what the actual pitfalls are.

Citations

WHO Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing. WHO-RUSH Human genome editing 1st advisory committee VPC. News conference, March 19, 2019.

E. Lander et al. Adopt a moratorium on heritable genome editing. Nature. Vol. 567, March 14, 2019, p. 165. doi: 10.1038/d41586-019-00726-5

Further Reading

T.H. Saey. Geneticists push for a 5-year global ban on gene-edited babies. Science News Online, March 13, 2019.

T.H. Saey. News of the first gene-edited babies ignited a firestorm. Science News. Vol. 194, December 22, 2018, p. 20.

T.H. Saey. Researchers say CRISPR edits to a human embryo worked. But critics still doubt it. Science News Online, August 8, 2018.

T.H. Saey. Human gene editing therapies are OK in certain cases, panel advises. Science News. Vol. 191, March 18, 2017, p. 7.

T.H. Saey. Human gene editing research gets green light. Science News. Vol. 188, December 26, 2015, p. 12.

https://www.sciencenews.org/article/nobel-prize-winner-david-baltimore-crispr-babies-ban

Cellectis: FDA Clears IND for 1st Allogeneic CAR-T for Multiple Myeloma

Cellectis, a biopharmaceutical company focused on developing immunotherapies based on gene-edited CAR T-cells (UCART), announced today that the U.S. Food and Drug Administration (FDA) has approved the Company’s Investigational New Drug (IND) application to initiate a Phase 1 clinical trial for UCARTCS1, in patients with multiple myeloma (MM). The IND for UCARTCS1 was filed on December 28, 2018 and approved by the FDA within a month, on January 25, 2019. Cellectis is the sponsor of the UCARTCS1 clinical study (MUNDI-01) and successfully ensured the manufacturing and release of UCARTCS1 GMP batches, as well as an IRB approval.

UCARTCS1 is based on a tailored manufacturing process developed by Cellectis, which removes both the CS1 antigen and TCR from the T-cell surface using TALEN^® gene editing technology, before adding the CS1 CAR construct. This approach has both clinical and operational benefits: the UCART is designed to have a lymphodepleting effect, and the CAR T-cell cross reaction is suppressed, allowing for successful manufacturing.

UCARTCS1 is the first allogeneic CAR-T therapy for MM to enter clinical development. This milestone reinforces Cellectis’ leadership in the space, as it represents the fourth TALEN^® gene-edited allogeneic CAR-T product candidate developed by Cellectis to be approved for clinical trials following UCART19¹ for ALL patients, UCART123 for AML patients and UCART22 for B-ALL patients. The Phase 1 of the MUNDI-01 study is designed to assess the safety and tolerability at increasing dose levels of UCARTCS1 in patients living with MM.

“The last quarters have been very productive for Cellectis’ UCARTCS1 product candidate. We successfully manufactured and released GMP batches of UCARTCS1, filed an IND and secured approval from the FDA to start the MUNDI-01 Phase 1 clinical study,” said Dr. André Choulika, Chairman and CEO of Cellectis. “This is the 4^th time in 4 years that Cellectis demonstrates excellence with an allogeneic product candidate. It further demonstrates the strength of our innovation, our manufacturing process and our execution, as we are eager to bring the first allogeneic multiple myeloma CAR T-cell treatment to patients.”

https://www.marketscreener.com/CELLECTIS-42457/news/Cellectis-FDA-Clears-the-IND-for-UCARTCS1-the-First-Allogeneic-CAR-T-to-Treat-Multiple-Myeloma-Pa-28341063/

Purdue’s Sackler family fights ‘inflammatory’ Massachusetts opioid case

Members of the Sackler family behind OxyContin maker Purdue Pharma LP have asked a judge to toss a lawsuit by Massachusetts’ attorney general claiming they helped fuel the U.S. opioid epidemic, arguing it contains “misleading and inflammatory allegations.”

The wealthy family in a motion on Monday argued that Massachusetts Attorney General Maura Healey, who brought the suit, had mischaracterized internal records to create the “false impression” they personally directed privately-held Purdue’s marketing of painkillers.

Her lawsuit, filed in June in Suffolk County Superior Court and revised earlier this year to include new allegations, was the first by a state to try to hold Sackler family members personally responsible for contributing to the opioid epidemic.

The case is among roughly 2,000 lawsuits filed by state and local governments seeking to hold Purdue and other pharmaceutical companies responsible for the U.S. opioid crisis.

Opioids were involved in a record 47,600 overdose deaths in 2017 in the United States, according to the U.S. Centers for Disease Control and Prevention.

Healey’s complaint cites records to argue that family members, including Purdue’s former President Richard Sackler, personally directed deceptive opioid marketing while making $4.2 billion from Purdue from 2008 to 2016.

They did so even after Purdue and three executives in 2007 pleaded guilty to federal charges related to the misbranding of OxyContin and agreed to pay a total of $634.5 million in penalties, the lawsuit said.

But in their motion, the Sacklers said nothing in the complaint supports allegations they personally took part in efforts to mislead doctors and the public about the benefits and addictive risks of opioids.

They said their role was limited to that of typical corporate board members who participated in “routine” votes to ratify the management’s staffing and budget proposals.

“Not a single document shows an individual director engaging in any unlawful conduct regarding the sale of prescription opioids or ordering anyone else to do so,” the Sacklers’ lawyers wrote.

Healey’s office had no comment.

At least 35 states have cases pending against Purdue. A handful have also named Sackler family members as defendants, including Richard Sackler, Theresa Sackler and Mortimer D.A. Sackler.

Last week, Purdue reached its first settlement in the recent wave of lawsuits, agreeing with the Sacklers to a $270 million deal with Oklahoma’s attorney general. The Sacklers were not named as defendants in Oklahoma’s lawsuit.

Purdue had been exploring filing for bankruptcy before the accord’s announcement, Reuters reported in early March.

https://www.marketscreener.com/news/Purdue-s-Sackler-family-fights-inflammatory-Massachusetts-opioid-case–28340701/?countview=0

Gritstone presents data on indentifying MHC class 2 antigens at AACR

Gritstone Oncology announced the presentation of data demonstrating its ability to identify major histocompatibility complex, or MHC, class 2 antigens at the American Association for Cancer Research, or AACR. In an oral presentation, it was shown that Gritstone Edge improved the positive predictive value for human leukocyte antigen class II, or HLA-DR, peptide presentation over standard methods by approximately 20-fold. Edge is an artificial intelligence platform that identifies tumor-specific neoantigens, or TSNA, for the development of antigen-directed immunotherapies that may drive highly specific tumor cell destruction by T cells. TSNA can be presented by either MHC class I, which are recognized by CD8 T cells, or MHC class II, which are recognized by CD4 T cells. The public tools available to predict tumor-specific antigens presented by MHC class I are more advanced; historically, the characterization of MHC class II presented antigens has been challenging for the field due to greater variability in their binding properties. The MHC class II dataset for the AACR analyses was derived from 73 human tumor and cell-line samples, including non-small cell lung cancer, lymphoma and ovarian cancer. The data sat is comprised over forty-five thousand tumor-presented peptides. Building on the progress with class I Edge, Gritstone’s class II model overcame a challenge with HLA class II prediction, which is the longer and more variable presented peptide lengths. Gritstone addressed this challenge with the new comprehensive training dataset and an innovative neural network architecture, leading to an approximately 20-fold increase in performance when using Edge versus standard methods. This dataset complements the previously reported Edge data demonstrating that it is approximately nine-fold better than publicly available tools at predicting tumor-specific antigens presented by MHC class I.
https://thefly.com/landingPageNews.php?id=2887651

Akebia selloff on ‘stale’ safety concern an overreaction, says Raymond James

Raymond James analyst Reni Benjamin attributes the selloff today in shares of Therapeutics to “stale” vadadustat safety concerns. After speaking with management the analyst views the selloff as an overreaction.
https://thefly.com/landingPageNews.php?id=2887649