Bryan Smith, an associate professor of biomedical engineering at Michigan State University and associates at Stanford University, developed a type of nanoparticle
that can “eat debris” related to the plaques that cause heart attacks.
They dub it a type of Trojan Horse and believe it has the potential to
treat atherosclerosis, a top cause of death in the U.S. The research was
published in the journal Nature Nanotechnology.
Atherosclerosis is hardening and narrowing of the arteries, which can
lead to heart attack or stroke. The plaques are made up of fat,
cholesterol, calcium and other substances in the blood.
Smith’s nanoparticles are based on single-walled carbon nanotubes
that are loaded with a chemical inhibitor of the antiphagocytic
CD47-SIRPĪ± signaling axis. In other words, the nanoparticle targets
atherosclerotic plaques because it has a high affinity to a particular
type of immune cell, monocytes and macrophages. Once the nanoparticle is
inside the plaque’s macrophages, it delivers the drug that causes the
cell to engulf and eat cellular debris.
“We found we could stimulate the macrophages to selectively eat dead
and dying cells—these inflammatory cells are precursor cells to
atherosclerosis—that are part of the cause of heart attacks,” Smith
said. “We could deliver a small molecule inside the macrophages to tell
them to begin eating again.”
The research team believes that future clinical trials with the
nanoparticles will decrease the risk of most forms of heart attacks with
minimal side effects. The minimal side effects are because of the
nanoparticle’s unusual degree of selectivity.
This is because Smith’s research is built on identifying and
intercepting the macrophage receptor signals and using a small molecule
from its nano-immunotherapeutic platforms to send messages. Other
research interacted with molecules on the cell surface, but this
approach works intracellularly.
The investigators believe the technology has applications beyond atherosclerosis.
“We were able to marry a groundbreaking finding in atherosclerosis by
our collaborators with the state-of-the-art selectivity and delivery
capabilities of our advanced nanomaterial platform,” Smith said.
He went on to add, “We demonstrated the nanomaterials were able to
selectively seek out and deliver a message to the very cells needed. It
gives a particular energy to our future work, which will include
clinical translation of these nanomaterials using large animal models
and human tissue tests. We believe it is better than previous methods.”
Current treatments for atherosclerosis include lifestyle changes such
as heart-healthy diets, losing weight, managing stress, exercise and
quitting smoking. Decreasing blood cholesterol levels using drugs, such
as statins, are often used, or in extreme cases, PCSK9 inhibitors. If it
becomes severe enough, there are several medical procedures such as
coronary angioplasty, which opens blocked or narrowed cardiac arteries,
or surgery such as coronary artery bypass grafting (CABG) or carotid
endarterectomy, which is surgery to remove the plaque buildup in the
carotid arteries in the neck.
Smith has filed a provisional patent for the nanoparticle device and expects to begin marketing it later this year.
https://www.biospace.com/article/nanoparticles-that-eat-away-the-plaques-that-cause-heart-attacks/
Wednesday, January 29, 2020
Following Patient Death, Spring Bank Abandons Hepatitis B Program
Spring Bank Pharmaceuticals, based in Hopkinton, Massachusetts, announced
it was discontinuing development of inarigivir soproxil for chronic
hepatitis B virus (HBV). The therapy was in Phase II development.
The company based the decision on safety information after unexpected serious adverse events, including one patient death in its Phase IIb CATALYST trial. Inarigivir is an orally available immunomodulator that binds the cellular proteins retinoic acid-inducible gene 1 (RIG-1) to inhibit viral replication and induce the intracellular interferon signaling pathways.
“We are deeply saddened by the death of a patient in our CATALYST 2 trial,” said Martin Driscoll, president and chief executive officer of Spring Bank. “Because we are guided by an overriding interest in protecting patients, we have made the difficult decision to discontinue the further development of inarigivir for the treatment of HBV at Spring Bank. We will continue to work in close collaboration with external experts and our clinical study investigators to provide the care necessary for all study patients and will continue to conduct a series of investigative actions to better understand the unexpected serious adverse events observed in our Phase IIb program.”
On December 26, 2019, the company indicated it had halted dosing and enrolling patients in the CATALYST trial as well as all other studies of inarigivir in chronic HBV. Lab tests from three patients showed hepatocellular dysfunction and an increased alanine transaminase (ALT) level consistent with liver injury.
It essentially plans to abandon R&D into HBV but will refocus on immuno-oncology and inflammation. This is primarily its lead product candidate from its STING agonist platform, SB 11285, which is in a Phase Ia/Ib trial.
On November 20, 2019, Spring Bank announced it had begun dosing patients in the Phase I trial of SB 11285 in patients with advanced solid tumors. Part 1 of the trial is a dose-escalation study with SB 11285 alone. It will be followed by a combination with a checkpoint inhibitor. Part 2 of the trial will evaluate intravenous SB 11285 antitumor activity in combination with a checkpoint inhibitor in various tumor types. The company hopes to report topline data in mid-2020.
“Working with our principal investigators in the United States, we are thrilled to announce that we have been able to deliver SB 11285 intravenously to the first patient in our Phase I trial of advanced solid tumors,” said Atif Abbas, vice president and head of Oncology/Immunology Development at Spring Bank, at the time.
He went on to say, “We believe the primary benefit of delivering SB 11285 by the intravenous route, as opposed to intratumorally like other STING agonist compounds currently in development, is the potential ability to treat a broader range of cancers and patients in the community oncology treatment setting.”
Now that Spring Bank is halting all HBV drug development, it is launching talks with external parties to license the program. And by eliminating the costs related to the HBV program, it believes it has funds to continue operations into late 2022. As of December 31, 2019, the company reported $54.5 million in cash.
https://www.biospace.com/article/spring-bank-pharma-discontinues-hepatitis-b-drug-development/
The company based the decision on safety information after unexpected serious adverse events, including one patient death in its Phase IIb CATALYST trial. Inarigivir is an orally available immunomodulator that binds the cellular proteins retinoic acid-inducible gene 1 (RIG-1) to inhibit viral replication and induce the intracellular interferon signaling pathways.
“We are deeply saddened by the death of a patient in our CATALYST 2 trial,” said Martin Driscoll, president and chief executive officer of Spring Bank. “Because we are guided by an overriding interest in protecting patients, we have made the difficult decision to discontinue the further development of inarigivir for the treatment of HBV at Spring Bank. We will continue to work in close collaboration with external experts and our clinical study investigators to provide the care necessary for all study patients and will continue to conduct a series of investigative actions to better understand the unexpected serious adverse events observed in our Phase IIb program.”
On December 26, 2019, the company indicated it had halted dosing and enrolling patients in the CATALYST trial as well as all other studies of inarigivir in chronic HBV. Lab tests from three patients showed hepatocellular dysfunction and an increased alanine transaminase (ALT) level consistent with liver injury.
It essentially plans to abandon R&D into HBV but will refocus on immuno-oncology and inflammation. This is primarily its lead product candidate from its STING agonist platform, SB 11285, which is in a Phase Ia/Ib trial.
On November 20, 2019, Spring Bank announced it had begun dosing patients in the Phase I trial of SB 11285 in patients with advanced solid tumors. Part 1 of the trial is a dose-escalation study with SB 11285 alone. It will be followed by a combination with a checkpoint inhibitor. Part 2 of the trial will evaluate intravenous SB 11285 antitumor activity in combination with a checkpoint inhibitor in various tumor types. The company hopes to report topline data in mid-2020.
“Working with our principal investigators in the United States, we are thrilled to announce that we have been able to deliver SB 11285 intravenously to the first patient in our Phase I trial of advanced solid tumors,” said Atif Abbas, vice president and head of Oncology/Immunology Development at Spring Bank, at the time.
He went on to say, “We believe the primary benefit of delivering SB 11285 by the intravenous route, as opposed to intratumorally like other STING agonist compounds currently in development, is the potential ability to treat a broader range of cancers and patients in the community oncology treatment setting.”
Now that Spring Bank is halting all HBV drug development, it is launching talks with external parties to license the program. And by eliminating the costs related to the HBV program, it believes it has funds to continue operations into late 2022. As of December 31, 2019, the company reported $54.5 million in cash.
https://www.biospace.com/article/spring-bank-pharma-discontinues-hepatitis-b-drug-development/
Illumina EPS beats by $0.12, beats on revenue
Revenue of $953M (+9.9% Y/Y) beats by $2.84M.
https://seekingalpha.com/news/3535973-illumina-eps-beats-0_12-beats-on-revenueAlign Tech down 9% despite Q4 beat as coronavirus creates headwinds in China
Align Technology (NASDAQ:ALGN) Q4 results:
Revenues: $649.8M (+21.7%); Clear Aligner sales: $543.6M (+22.0%); Scanner & Services: $106.2M (+20.1%).
Invisalign case shipments: 413.7K (+23.9%).
Net income: $121.3M (+24.5%); EPS: $1.53 (+27.5%).
Cash flow ops (full year): $747.3M (+34.7%).
Q1 guidance: Revenues: $615.0M –
630.0M (includes the impact in China cited below). Invisalign case
shipments: 396K – 406K; EPS: $18.65 – 18.74; non-GAAP EPS: $1.19 – 1.28.
Reduction of 20K – 25K Invisalign case shipments
and $30M – 35M less Invisalign and iTero revenue in China due to
coronavirus outbreak. Gross margin will be negatively impacted by 0.5%
due to the absorption of $3.0M – 4.0M in idle plant capacity costs in
China.
https://seekingalpha.com/news/3536012-align-tech-down-9-despite-q4-beat-coronavirus-creates-headwinds-in-chinaVarian Medical Systems EPS misses by $0.04, revenue in-line
Varian Medical Systems (NYSE:VAR): Q1 Non-GAAP EPS of $1.16 misses by $0.04; GAAP EPS of $0.96 misses by $0.09.
Revenue of $828.9M (+11.9% Y/Y) in-line.
https://seekingalpha.com/news/3535985-varian-medical-systems-eps-misses-0_04-revenue-in-lineImmutep up 21% ahead of key data readouts
Thinly traded nano cap Immutep Limited (IMMP +19%) is up on a 14x surge in volume on the heels of its pipeline update including several important near-term data readouts.
Lead candidate eftilagimod alpha (“efti”): progression-free survival (PFS) data expected in March from the pivotal AIPAC
study evaluating efti + paclitaxel in 227 HR+ metastatic breast cancer
patients. Key secondary endpoints are overall survival (OS) and overall
response rate (ORR).
The company is planning to conduct a 24-subject bridging study assessing the combination in metastatic breast cancer patients.
Preliminary results from another Phase 2 study, TACTI-002,
evaluating efti + Merck’s Keytruda (pembrolizumab) in NSCLC and head
and neck squamous cell carcinoma (HNSCC) patients showed an ORR of 41%.
More mature data are expected next month.
Eftilagimod alpha is LAG-3
fusion protein designed to boost T cell responses to cancer. LAG-3
(lymphocyte activation gene-3) plays a key role in regulating the immune
system, specifically, signaling between T cells and antigen-presenting
cells which are responsible for the adaptive immune response.
https://seekingalpha.com/news/3535950-immutep-up-21-ahead-of-key-data-readoutsAnthem Falls on Weak Metric, Disappointing 2020 Guidance
Shares in Anthem Inc. tumbled on Wednesday after the health insurer
reported a key spending metric came in higher than analysts had expected
in the fourth quarter, and its financial forecast for this year also
disappointed.
The stock was down 4.5% in early-afternoon trading on the New York Stock Exchange after the insurer reported its 2019 earnings, though the company posted higher fourth-quarter revenue and profit.
The health insurer recorded a profit of $934 million, or $3.62 a share, in the fourth quarter of 2019 compared with $424 million, or $1.61 a share, in the year-ago quarter. Adjusted earnings were $3.88 a share, matching analysts’ expectations.
Revenue was $27.41 billion, up from $23.37 billion.
Anthem Chief Executive Gail Boudreaux said in a conference call that the company was delivering on its promised growth and was “poised for another year of success in 2020.”
Investors focused on Anthem’s medical-loss ratio, or MLR, which represents the share of premiums the insurer pays out in claims. They closely watch the MLR as a gauge of health spending and insurers’ operational profitability, and get nervous when it ticks up unexpectedly.
Anthem said its MLR was 89% in the fourth quarter, higher than the 88.1% figure that a consensus of analysts had estimated. The insurer said the figure was pushed up compared with last year due to the suspension of a tax on health insurers, an industrywide effect analysts had expected. But Anthem flagged other factors as well, including higher-than-expected health costs tied to the flu.
Another Wall Street concern was Anthem’s new 2020 guidance, which projected earnings of more than $21.44 a share, including about 86 cents a share of net unfavorable items.
The Indianapolis-based company estimated 2020 adjusted earnings of more than $22.30 a share. That figure, which excludes the effects of amortization and some other factors, was lower than many analysts had anticipated based on early projections Anthem offered last quarter.
Executives attributed the shortfall to the coming repeal of the health-insurance tax, passed late last year. Like other insurers, Anthem had passed through this tax to customers in the form of higher premiums.
The company expects the repeal of the tax will pull down earnings this year, even though the repeal doesn’t take effect until 2021, because some clients renew their coverage midyear. Anthem said it hadn’t factored that effect into the broad early guidance that it previously issued.
Chief Financial Officer John Gallina said the company’s core assumptions for its 2020 performance hadn’t changed, except for the impact of the 2021 health-tax repeal. He said that dynamic would affect 2020 earnings by around 30 cents per share.
Anthem is among the biggest health insurers in the U.S. One bright sign for the company was its projection for medical costs for fully insured employer plans, which Anthem estimates will increase around 4% in 2020, down from the current rate of around 6%.
The insurer attributed the expected drop to the effects of its newly launched pharmacy-benefit manager, IngenioRx, and other cost-reduction efforts.
In the conference call, Mr. Gallina attributed the company’s higher MLR ratio partly to an early start to the flu season.
He also said Anthem now expects to receive a smaller payout than it originally projected from an Affordable Care Act program, which hurt its MLR result.
The biggest driver of the 2019 MLR performance, Mr. Gallina said, was last year’s suspension of the health-insurance tax, an issue which affects all insurers. The tax, a pass-through, had effectively increased the revenue part of the MLR ratio in previous years because insurers added it to premiums charged.
The tax is set to return next year, but has been repealed effective in 2021. lt affects 2020 results because some clients renew their coverage plans partway through the calendar year, and their monthly premiums would reflect the coming change.
Given the tax’s return, Mr. Gallina said Anthem expects the MLR for 2020 will be lower than last year.
Yet he said the drop will be smaller than it otherwise would have been, due to factors including the company’s changing mix of business, which includes a higher proportion of enrollees in government plans such as Medicaid. The ratio tends to be higher in government plans.
https://www.marketscreener.com/ANTHEM-INC-18740543/news/Anthem-Falls-on-Weak-Metric-Disappointing-2020-Guidance-29909219/
The stock was down 4.5% in early-afternoon trading on the New York Stock Exchange after the insurer reported its 2019 earnings, though the company posted higher fourth-quarter revenue and profit.
The health insurer recorded a profit of $934 million, or $3.62 a share, in the fourth quarter of 2019 compared with $424 million, or $1.61 a share, in the year-ago quarter. Adjusted earnings were $3.88 a share, matching analysts’ expectations.
Revenue was $27.41 billion, up from $23.37 billion.
Anthem Chief Executive Gail Boudreaux said in a conference call that the company was delivering on its promised growth and was “poised for another year of success in 2020.”
Investors focused on Anthem’s medical-loss ratio, or MLR, which represents the share of premiums the insurer pays out in claims. They closely watch the MLR as a gauge of health spending and insurers’ operational profitability, and get nervous when it ticks up unexpectedly.
Anthem said its MLR was 89% in the fourth quarter, higher than the 88.1% figure that a consensus of analysts had estimated. The insurer said the figure was pushed up compared with last year due to the suspension of a tax on health insurers, an industrywide effect analysts had expected. But Anthem flagged other factors as well, including higher-than-expected health costs tied to the flu.
Another Wall Street concern was Anthem’s new 2020 guidance, which projected earnings of more than $21.44 a share, including about 86 cents a share of net unfavorable items.
The Indianapolis-based company estimated 2020 adjusted earnings of more than $22.30 a share. That figure, which excludes the effects of amortization and some other factors, was lower than many analysts had anticipated based on early projections Anthem offered last quarter.
Executives attributed the shortfall to the coming repeal of the health-insurance tax, passed late last year. Like other insurers, Anthem had passed through this tax to customers in the form of higher premiums.
The company expects the repeal of the tax will pull down earnings this year, even though the repeal doesn’t take effect until 2021, because some clients renew their coverage midyear. Anthem said it hadn’t factored that effect into the broad early guidance that it previously issued.
Chief Financial Officer John Gallina said the company’s core assumptions for its 2020 performance hadn’t changed, except for the impact of the 2021 health-tax repeal. He said that dynamic would affect 2020 earnings by around 30 cents per share.
Anthem is among the biggest health insurers in the U.S. One bright sign for the company was its projection for medical costs for fully insured employer plans, which Anthem estimates will increase around 4% in 2020, down from the current rate of around 6%.
The insurer attributed the expected drop to the effects of its newly launched pharmacy-benefit manager, IngenioRx, and other cost-reduction efforts.
In the conference call, Mr. Gallina attributed the company’s higher MLR ratio partly to an early start to the flu season.
He also said Anthem now expects to receive a smaller payout than it originally projected from an Affordable Care Act program, which hurt its MLR result.
The biggest driver of the 2019 MLR performance, Mr. Gallina said, was last year’s suspension of the health-insurance tax, an issue which affects all insurers. The tax, a pass-through, had effectively increased the revenue part of the MLR ratio in previous years because insurers added it to premiums charged.
The tax is set to return next year, but has been repealed effective in 2021. lt affects 2020 results because some clients renew their coverage plans partway through the calendar year, and their monthly premiums would reflect the coming change.
Given the tax’s return, Mr. Gallina said Anthem expects the MLR for 2020 will be lower than last year.
Yet he said the drop will be smaller than it otherwise would have been, due to factors including the company’s changing mix of business, which includes a higher proportion of enrollees in government plans such as Medicaid. The ratio tends to be higher in government plans.
https://www.marketscreener.com/ANTHEM-INC-18740543/news/Anthem-Falls-on-Weak-Metric-Disappointing-2020-Guidance-29909219/
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